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PubMed1999

Development of a sensitive enzymeimmunoassay (EIA) for FSH determination in bovine plasma.

A highly sensitive enzymeimmunoassay (EIA) procedure for FSH determination in bovine plasma on microtiterplates using the biotin-streptavidin amplification system and the second antibody coating was developed. Biotin was coupled to FSH and used to bridge between streptavidin-peroxidase and the immobilized antiserum in the competitive assay. The EIA was carried out directly in 50 microl of bovine plasma and compared with an established radioimmunoassay (RIA) employing 100 microl plasma. Same FSH standards and FSH specific antiserum were used in both procedures. FSH standards prepared in hormone free plasma were used. The sensitivity of the EIA procedure was 6.25 pg/well FSH which corresponded to 125 pg/ml plasma; the 50% relative binding sensitivity was seen at 200 pg/well. In comparison to RIA, the EIA was at least four times more sensitive besides requiring 6 times less FSH specific antiserum. Plasma volumes for the EIA ranging from 12.5 to 50 microl did not influence the shape of the standard curve even though a slight drop in the OD450 was seen with higher plasma volumes. When both EIA and RIA methods were used to measure FSH in cows, the levels were detectable only by the EIA procedure. The assay detects high and low plasma FSH levels within the physiological variation as well as changes in plasma FSH after stimulation with a GnRH analog. In conclusion, in addition to being non-radioactive and low cost in nature, the method offers several advantages over the conventional FSH RIA procedure; these are (a) higher sensitivity, (b) less labour and time saving, (c) more economical use of precious FSH antiserum and (d) long shelf-life of the biotinyl-FSH label (in contrast to the short half life of iodinated FSH in RIA).

Animals↗
PubMed1999

Estrogen and leptin have differential effects on FSH and LH release in female rats.

Prior experiments have shown that the adipocyte hormone leptin can advance puberty in mice. We hypothesized that it would also stimulate gonadotrophin secretion in adults. Since the secretion of follicle stimulating hormone (FSH) and luteinizing hormone (LH) is drastically affected by estrogen, we hypothesized that leptin might have different actions dependent on the dose of estrogen. Consequently in these experiments, we tested the effect of injection of leptin into the third cerebral ventricle of ovariectomized animals injected with either the oil diluent, 10 microg or 50 microg of estradiol benzoate 72 hr prior to the experiment. The animals were ovariectomized 3-4 weeks prior to implantation of a cannula into the third ventricle 1 week before the experiments. The day after implantation of an external jugular catheter, blood samples (0. 3 ml) were collected just before and every 10 min for 2 hr after 3V injection of 5 microl of diluent or 10 microg of leptin. Both doses of estradiol benzoate equally decreased plasma LH concentrations and pulse amplitude, but there was a graded decrease in pulse frequency. In contrast, only the 50-microg dose of estradiol benzoate significantly decreased mean plasma FSH concentrations without significantly changing other parameters of FSH release. The number of LH pulses alone and pulses of both hormones together decreased as the dose of estrogen was increased, whereas the number of pulses of FSH alone significantly increased with the higher dose of estradiol benzoate, demonstrating differential control of LH and FSH secretion by estrogen, consistent with alterations in release of luteinizing hormone releasing hormone (LHRH) and the putative FSH-releasing factor (FSHRF), respectively. The effects of intraventricularly injected leptin were drastically altered by increasing doses of estradiol benzoate. There was no significant effect of intraventricular injection of leptin (10 microg) on the various parameters of either FSH or LH secretion in ovariectomized, oil-injected rats, whereas in those injected with 10 microg of estradiol benzoate there was an increase in the first hr in mean plasma concentration, area under the curve, pulse amplitude, and maximum increase of LH above the starting value (Deltamax) on comparison with the results in the diluent-injected animals in which there was no alteration of these parameters during the 2 hr following injection. The pattern of FSH release was opposite to that of LH and had a different time-course. In the diluent-injected animals, probably because of the stress of injection and frequent blood sampling, there was an initial significant decline in plasma FSH at 20 min after injection, followed by a progressive increase with a significant elevation above the control values at 110 and 120 min. In the leptin-injected animals, mean plasma FSH was nearly constant during the entire experiment, coupled with a significant decrease below values in diluent-injected rats, beginning at 30 min after injection and progressing to a maximal difference at 120 min. Area under the curve, pulse amplitude, and Deltamax of FSH was also decreased in the second hour compared to values in diluent-injected rats. In contrast to the stimulatory effects of intraventricular injection of leptin on pulsatile LH release manifest during the first hour after injection, there was a diametrically opposite, delayed significant decrease in pulsatile FSH release. This differential effect of leptin on FSH and LH release was consistent with differential effects of leptin on LHRH and FSHRF release. Finally, the higher dose of E2 (50 microg) suppressed release of both FSH and LH, but there was little effect of leptin under these conditions, the only effect being a slight (P < 0.04) increase in pulse amplitude of LH in this group of rats. The results indicate that the central effects of leptin on gonadotropin release are strongly dependent on plasma estradiol levels. These effects are consistent w

Activity Cycles↗
PubMedDate not supplied

Urinary beta-FSH subunit concentrations in perimenopausal and postmenopausal women: a biomarker for ovarian reserve.

OBJECTIVE: The purpose of this study was to develop an integrative assessment of pituitary follicle-stimulating hormone (FSH) secretion and to validate these measurements in a population of perimenopausal (PERI) and postmenopausal (POST) women. DESIGN: In this cross-sectional study, 170 POST and 20 PERI women collected first-void morning urine samples and had a single blood sample drawn on the same day. For comparison, 11 midreproductive-aged women had urine samples collected for one menstrual cycle. In addition, one 48.5-year-old woman collected daily urine samples for 4 consecutive years during her menopausal transition. Urine samples were assayed for estrone glucuronide (E1G) and pregnanediol-3-glucuronide (PdG) and were normalized to creatinine. An ELISA assay was developed for measurement of the free beta-FSH subunit in urine. RESULTS: Mean age (+/- SD) of the PERI and POST women were 48.1 +/- 3.0 and 52.8 +/- 4.1 years, respectively. Mean serum FSH levels were 9.5 +/- 5.8 and 79.3 +/- 32 IU/L (P < 0.001) in the PERI and POST women. Mean urinary beta-FSH/Cr for the PERI were 1.8 +/- 1.2 ng/mg; for the POST, 9.3 +/- 4.5 ng/mg (P < 0.001). Mean estradiol, E1G/Cr, and PdG/Cr levels were also significantly different between the two groups. There was a high correlation between serum FSH and urinary beta-FSH/Cr for the PERI (r = 0.584, P = 0.007) and POST (r = 0.54, P < 0.001), with minimal overlap in the urinary beta-FSH/Cr levels between the PERI and POST groups. A significant correlation between PdG/Cr and urinary beta-FSH/Cr was observed for POST (r = 0.581, P = 0.002). No correlation was seen between urinary beta-FSH/Cr and E1G/Cr or estradiol levels. In the perimenopausal participant, who collected 4 years of daily urine samples, urinary beta-FSH/Cr levels progressively increased during the follicular phase and, by the fourth year, there were persistent, almost tonically high elevations of beta-FSH/Cr in the urine. CONCLUSIONS: Urinary beta-FSH subunit measurements are a useful marker for monitoring ovarian function during the menopausal transition. Urinary free beta-FSH subunit concentrations reflect pituitary FSH secretion and serve as a biomarker for ovarian reserve.

Climacteric↗
PubMed1981

Possible existence of a long-loop feedback system between FSH and inhibin in female rats.

Experiments were designed in which peripheral plasma inhibin levels were presumably altered in an attempt to investigate an interdependency between pituitary follicle-stimulating hormone (FSH) and ovarian inhibin secretion. In the first study, unilateral ovariectomy (ULO) was performed on 4-day cycling female rats under ether anesthesia at 0800 h on diestrous day 1 (D1). Inhibin-like activity [FSH-inhibiting activity(FSH-IA)] in untreated ovarian venous plasma (OVP) collected from the remaining ovary was assessed by an in vitro pituitary bioassay system. Both plasma FSH levels and FSH-IA significantly increased between 4 and 12 h after ULO. Thereafter, plasma FSH declined between 12 and 32 h after ULO, whereas FSH-IA remained elevated during this same time interval. Compared to sham-operated rats, plasma FSH was significantly elevated 4, 12, and 24 h after ULO, whereas FSH-IA was statistically higher only at 32 h after ULO. In a second experiment, rats were injected with charcoal-treated porcine follicular fluid (PFF) on proestrus and estrus. Control rats received saline. The data indicate that increased plasma FSH levels on D1 in PFF-treated rats (FSH rebound) may be a consequence of reduced endogenous inhibin secretion on estrus. As well, return of FSH to control levels on D2 in PFF-treated rats may have resulted from an FSH-associated increase in FSH-IA on D1 and D2.

Animals↗
PubMed1996

Growth of differentiation: determination by FSH of the action of insulin-like growth factor-I in cultured rat granulosa cells.

Insulin-like growth factor-I (IGF-I) is a potent mitogen in many cell systems. In cultured rat granulosa cells, however, IGF-I is known to be an inducer of differentiation. The present study was conducted to identify the factor which determines the direction of IGF-I action: either DNA synthesis or LH receptor expression. When granulosa cells were incubated with IGF-I in the presence of various concentrations of follicle-stimulating hormone (FSH), DNA synthesis as assessed by [3H]thymidine incorporation was increased only in the presence of low doses of FSH. The stimulatory effect of FSH on DNA synthesis was observed in a very narrow range of FSH concentration between 2 and 10 ng/ml. At higher concentrations, FSH had little effect on DNA synthesis but instead induced expression of receptors for luteinizing hormone (LH), a marker of granulosa cell differentiation. At 5 ng/ml, FSH elicited maximal stimulation of DNA synthesis and simultaneously induced LH receptor expression to some extent. In these cells, DNA synthesis peaked at 36 h but expression of LH receptor occurred later than 36 h, peaking at 60 h. The ability of IGF-I to stimulate DNA synthesis was enhanced by the long term pretreatment with FSH: when FSH was added from the beginning and IGF-I was added after 36 h or later, IGF-I-mediated DNA synthesis was approximately twice as great, and was accompanied by a two-fold increase in the number of bromodeoxyuridine-labeled nuclei. Under these conditions, LH receptor expression was reduced to approximately 50%. Finally when cells were incubated for 12 h with or without FSH, washed extensively with the medium and then IGF-I was added, DNA synthesis was augmented only in FSH-primed cells. Forskolin, an activator of adenylate cyclase, reproduced the effect of FSH. These results indicate that, in the presence of FSH, IGF-I has the ability to induce both DNA synthesis and differentiation and that FSH determines the action of IGF-I on promotion of either growth or differentiation. Furthermore, priming with FSH renders granulosa cells responsive to IGF-I in terms of DNA synthesis.

Animals↗
PubMed1980

FSH-response adenylyl cyclase in rat testes: desensitization by homologous hormone.

Injection of high doses of FSH causes a partial desensitization of the FSH-responsive adenylyl cyclase (AC) in adult rat testes. The loss of responsiveness to FSH is dependent on time. Two hours after injection of one dose of human FSH (256 micrograms hFSH-PT2) in vivo, no effect was seen on FSH-stimulated AC activity (Km and maximal activation). After 24 hr there was an approximately 40% decrease in FSH activated AC. Injection of two doses of FSH (256 micrograms hFSH-PT2) 24 and 48 hr before being killed, gave a loss in FSH-responsive AC activity of approximately 60%. The decreased FSH-stimulated AC activity after FSH injections in vivo was associated with a comparable decrease in specific FSH binding. Whether this is a reflection of receptor occupancy or down regulation of the number of FSH receptors is not known. Desensitization of the FSH-responsive AC caused by FSH was not associated with a change in its Km.

Adenylyl Cyclases↗
PubMed2001

FSH secretion patterns during pregnant and nonpregnant luteal periods and 24 h secretion patterns in male and female dogs.

The aim of this study was to investigate the secretion patterns of FSH: (i) during the canine oestrous cycle with particular attention to the luteal period; and (ii) during 24 h in male and female dogs. Plasma FSH concentrations were measured by a highly specific homologous canine immunoradiometrical (IRMA) assay using monoclonal antibodies specific for canine FSH. In the first study, FSH concentrations were measured daily from +/- 15 days before until 150 days after the LH surge in groups of pregnant (n = 5) and nonpregnant (n = 5) Beagle bitches. Day 0 of the cycle was the day of the preovulatory LH peak as measured by LH radioimmunoassay. In the second study, FSH concentrations were measured at 1 h intervals for 24 h in five bitches at day 120 after the LH surge and in five males. From day 35 to day 40 after the LH peak, FSH concentrations were higher in pregnant than in nonpregnant luteal phases. A significant and abrupt decrease in FSH concentrations was observed at about the time of parturition (day 65) and was followed by lower FSH concentrations during lactation compared with nonpregnant bitches. FSH concentrations in nonpregnant animals were fairly constant from the end of oestrus to mid-anoestrus. In both post-lactation and anoestrous bitches, plasma concentrations of FSH increased consistently as anoestrus progressed. No significant differences in the mean hour-to-hour patterns of FSH secretion were observed over 24 h and no differences were detected between male and female dogs. However, a clear pulsatile pattern of secretion was observed in all individuals, both males and females, with an apparent 4.8 h interval between peaks. The results of this study demonstrate major differences in FSH secretion between pregnant and nonpregnant bitches. This finding indicates that there are differences in the regulation of the hypothalamo-pituitary-ovarian axis during pregnancy, possibly related to changes in activity of the corpus luteum. The results of this study also demonstrate a pulsatile pattern of FSH secretion in both male and female bitches, with a 4.8 h interval between peaks, and confirms the progressive increase in plasma FSH concentrations observed during anoestrus.

Animals↗
PubMed1997

Modulation of FSH receptor phosphorylation correlates with hormone-induced coupling to the adenylate cyclase system.

The authors have recently demonstrated that an inhibitor of protein phosphorylation, staurosporine (SSP), can dramatically enhance follicle-stimulating hormone (FSH) stimulated cyclic adenosine monophosphate (cAMP) accumulation in rat granulosa cell line (GFSHR-17) overexpressing about 20-fold FSH receptor than primary granulosa cells. Moreover, incubation with SSP can partially release the cells from FSH-induced desensitization. In this work, it was examined whether coupling of FSH receptor to the adenylate cyclase is correlated with the degree of receptor phosphorylation. Immunoprecipitation of FSH receptor after metabolic labeling of the cells with 32P-orthophosphate revealed that preincubation of the cells with SSP resulted in pronounced reduction in FSH receptor phosphorylation compared to control cells, concomitantly with a dramatic increase in FSH-stimulated cAMP accumulation. In contrast, incubation of the cells with saturating dose of FSH, which leads to uncoupling between the receptor and the adenylate cyclase, resulted in enhanced receptor phosphorylation. Moreover, cells preincubated with FSH could be released from desensitization by further incubation with SSP and a significant reduction in FSH receptor phosphorylation. Immunostaining of the cells with FSH receptor antibody reveal a homogenous distribution of the receptor on the surface of SSP-treated cells. Some aggregation of the receptor was evident in control cells that were not treated with SSP. In contrast, massive clustering and capping of the receptor molecules were observed on the surface of FSH-stimulated cells. The current data suggest that phosphorylation-dephosphorylation of the receptor molecules play an important role in the degree of coupling between the receptor and the adenylate cyclase system. Moreover, desensitization to FSH stimulation that is implicated with high degree of receptor phosphorylation may lead to aggregation of the receptor molecules on the cell surface.

Adenylyl Cyclases↗
PubMed1998

FSH bioactivity in commercial preparations of gonadotropins.

During the past 2 decades, commercial preparations of FSH have been extensively used to superovulate cattle. The problems that have been encountered in superovulation of cattle include high variability in the ovulation rate and subsequent yield of viable embryos. The lack of predictability in superovulatory trials has been attributed to difficulties in standardizing the potency of commercial FSH preparations. Traditionally, FSH potency has been tested in bioassays that utilize specific responses in whole animals or primary cell cultures. Whole animal bioassays lack sensitivity, while primary cell culture bioassays, which use fresh cells, have inherent variability within each preparation. An FSH bioassay that employed a stable chimeric cell line expressing the human FSH-R was used to provide an accurate measurement of FSH bioactivity. The hormonal potency of 2 commercial preparations of FSH used to superovulate cattle was determined using FSH immuno- and bioassays. Commercial FSH preparations differed in potency. One commercial product, prepared in 4 different years, showed no difference in the immunoactive levels of FSH. In the same product stored under identical conditions, FSH bioactivity varied from year to year. There was variability in FSH bioactivity both between and within commercial products. The lack of correlation between bioactivity and immunoactivity of commercial FSH preparations may explain, in part, the variability observed in superovulation of cattle.

Animals↗
PubMed1997

Transcriptional and post-transcriptional regulation of FSH receptor in rat granulosa cells by cyclic AMP and activin.

The effect of FSH on the induction of FSH receptors in granulosa cells is believed to be mediated, at least in part, by the cAMP second messenger system. We examined the effect of activin and cAMP on FSH receptor expression in this culture system. Steady-state levels of FSH receptor mRNA, analyzed by Northern blot hybridization, increased 3.5-fold in response to 24-h incubation with activin and 1.7-fold with 12-h incubation with 8-bromoadenosine 3,5-cyclic monophosphate (8-Br-cAMP; 0.2 mM). We have investigated whether 8-Br-cAMP- and/or activin-induced increases in FSH receptor mRNA levels are the result of increased transcription and/or altered mRNA stability. The rates of FSH receptor mRNA gene transcription, assessed by nuclear run-on transcription assay, increased 3-fold in cells treated with activin and 1.5-fold in cells treated with 8-Br-cAMP for 2 h. To examine the degradation rates of FSH receptor mRNA transcripts, granulosa cells were preincubated with 8-Br-cAMP, activin, or medium alone for 6 h. After the preincubation period, 5 microM actinomycin-D or 200 microM 5,6-dichloro-1-beta-ribofuranosyl benzimidazole were added to arrest new RNA synthesis. The decay curves for the 2.4 kb FSH receptor mRNA transcript in granulosa cells were not significantly different in the absence or presence of 8-Br-cAMP. Activin, on the other hand, significantly altered the slope of the FSH receptor mRNA decay curve and increased the half-life of the 2.4 kb FSH receptor mRNA transcript. These data provide evidence that cAMP induces FSH receptor mRNA levels by stimulating the transcription rate and that activin increases FSH receptor mRNA levels both by stimulating transcription rates and by stabilizing the FSH receptor mRNA transcripts.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1997

Cumulus cells of oocyte-cumulus complexes secrete a meiosis-activating substance when stimulated with FSH.

The effect of the different follicular cell types on resumption of meiosis was studied during stimulation with FSH. Cumulus enclosed oocytes (CEO), denuded oocytes (DO), and cumulus and mural granulosa cells were used. The resumption of meiosis and oocyte maturation were assessed by the determination of the germinal vesicle breakdown (GVBD) and polar body formation (PB) at the end of a 24 hr culture period in the presence of 4 mM hypoxanthine (HX). The effects of recombinant LH (r-LH) and hCG were also evaluated. Oocyte exposure to the gonadotrophins varied from 5 min to 24 hr (i.e., priming time). Oocytes were obtained from immature gonadotrophin-stimulated and -unstimulated mice. 1. FSH (1 IU/L-75 IU/L) provoked a dose-dependent increase in GVBD and PB in CEO, but not in DO, in stimulated and unstimulated mice. Eight IU/L was sufficient for inducing resumption of meiosis. In contrast, LH and hCG (both 1 IU/L-1500 IU/L) were without effect on GVBD and PB in CEO and DO of oocytes from stimulated and unstimulated mice. A combination of 8 IU/L FSH and 4-8 IU/L hCG produced an additive effect, whereas combinations with LH and higher concentrations of hCG had no such effect. 2. A 2 hr priming with FSH (8 IU/L-75 IU/L) induced a dose-dependent oocyte maturation in CEO. Thirty minutes of priming with FSH (75 IU/L) was sufficient for induction of meiotic resumption in CEO. 3. Priming CEO with FSH for 2 hr followed by the separation and repooling of oocytes and cumulus cells induced oocyte maturation. GVBD of new, unprimed DO added to cumulus cells of primed CEO increased slightly but was significant, whereas GVBD in DO isolated from the primed CEO only increased marginally. DO cocultured with FSH-primed cumulus masses seem to be prevented from resuming meiosis. 4. Priming a coculture of granulosa cells and DO with FSH for 2 hr caused a significant increase in GVBD compared to the control, evaluated after 24 hr. In contrast, a 24 hr FSH-priming of a coculture of granulosa cells and DO was without effect on GVBD. 5. A spent medium in which unstimulated cumulus cells or mural granulosa cells had grown was without effect on GVBD in DO. However, a small fraction of the DO resumed meiosis after culture in a spent medium derived from a 2 hr priming of CEO and spent media from 24 hr priming of CEO induced a 2-3 times higher GVBD frequency in the DO compared to the controls. Heat treatment of spent media (70 degrees C, 30 min) from a 24 hr FSH-priming of CEO still induced GVBD in naive DO. The results showed that FSH, in a concentration of as little as 8 IU/L, but not r-LH and hCG, induced within 30 minutes the cumulus cells to produce and after 2 hr to secrete a diffusible heat stable meiosis activating substance. This substance overcame, in a paracrine fashion, the inhibiting effect of HX and induced oocyte maturation directly in DO. The production of this substance, however, was dependent on the initial connection between the cumulus cells and the oocyte, indicating an important 2-way communication between these 2 cell types. The mural granulosa cells did not produce a meiosis inducing activity by stimulation with FSH, but significantly, more DO matured after coculture with the nonstimulated granulosa cells for 24 hr than for 2 hr. It is proposed that the heat stable meiosis activating component of the spent media from the FSH-stimulated CEO belongs to the meiosis activating sterols, MAS, previously isolated from human follicular fluid and from adult bull testes.

Animals↗
PubMed1987

Selective modulation of FSH and LH secretion by steroids.

Significant divergence between the pattern of FSH and LH secretion has been observed in the ovulatory cycle, after ovariectomy and during puberty. The presence of an FSH-releasing factor, gonadal FSH inhibiting and releasing peptides and changes in the pulsatile pattern of LHRH secretion are among the postulates used to explain the divergent secretion of FSH and LH. Experiments in our laboratory have shown considerable evidence of differential regulation of FSH and LH secretion by steroids in the absence of gonadal regulatory peptides. Natural and synthetic estrogens show significant differences in the suppression of FSH and LH in the ovariectomized rat using a standard uterine response to the estrogen as the end point. In the immature ovariectomized rat treated with a low dose of estradiol that is sufficient for the synthesis of progesterone receptors to ensure progesterone sensitivity, but not large enough to induce estrogen triggered LH surges, progesterone administration resulted in a pattern of LH and FSH secretion similar to that observed on the day of proestrus in the cycling rat. Selective secretion of FSH was induced in the estrogen primed immature rat model by the administration of progesterone metabolite 5 alpha-dihydroporgesterone (5 alpha-DHP) while selective LH secretion was induced by 3 alpha, 5 alpha-tetrahydroprogesterone (3 alpha,5 alpha-THP). The selective secretion of FSH and LH induced by progesterone metabolites was confirmed in the immature female rat primed with PMSG and maintained in constant light. 5 alpha-DHP was also able to induce a greater release of FSH when administered to the adult cycling rat on proestrus. The priming of the pituitary gonadotrope in secreting a high baseline level of FSH or responding to LHRH in releasing a greater amount of FSH appeared to be an important factor in selective FSH release and such priming can be brought about by 5 alpha-DHP in the absence of gonadal regulatory peptides.

Animals↗
PubMed1989

Endocrine and superovulatory responses in heifers pretreated with FSH or bovine follicular fluid.

This study examined the effects of altered serum FSH concentration on subsequent ovarian response to superovulation. Synchronized heifers were assigned randomly on Day 1 of the cycle (estrus = Day 0) to three pretreatment groups that consisted of 6-d of saline (7ml, s.c., b.i.d.; Group I), FSH-P (0.5 mg, i.m., b.i.d.; Group II) or charcoal-extracted bovine follicular fluid (BFF; 7 ml, s.c., b.i.d.; Group III) injections. Superovulation was initiated on Day 7 and consisted of FSH-P in decreasing dosages over 4 d (4,3,2,1 mg; i.m., b.i.d.), with cloprostenol (500 mug) on the morning of the third day. A second replicate with 14 heifers was conducted using the same protocol but twice the pretreatment dosage of FSH-P (1 mg) and BFF (14 ml). Endogenous plasma FSH decreased during BFF and FSH-P pretreatments compared to controls (P < 0.02). Endogenous FSH concentrations in both primed groups (II and III) were similar to control values (Group I) 12 h after the start of superovulation. Basal LH concentrations were not different between pretreatment groups. The interval from cloprostenol treatment to the preovulatory LH surge in Group III was 21.3 and 23.9 h longer (P < 0.0001) than it was in Groups I and II. The postovulation progesterone rise was delayed in Group III. The number of corpora lutea (CL) was lowest in the BFF-primed group (4.2 +/- 0.8) compared with the FSH-primed (7.4 +/- 1.3) and the control (12.0 +/- 1.8; P < 0.003) groups. In the FSH-primed group (0.68 +/- 0.06 cm(3)), CL volumes were larger than in the control group (0.45 +/- 0.03 cm(3)), whereas in the BFF-primed group (0.27 +/- 0.02 cm(3)) CL volumes were smaller compared with the control group (P < 0.0001). Mean FSH concentrations for 48 h preceding superovulation and the number of CL per cow were positively correlated (r = 0.55; P < 0.004; n = 26). We concluded that both FSH-P and BFF pretreatments decreased the superovulatory response of heifers to FSH-P. The mechanism for this would appear to be associated with reduced endogenous FSH prior to the start of superovulation.

Journal Article↗
PubMed1992

Interrelationships of hormonal and ovarian responses in superovulated heifers pretreated with FSH-P at the beginning of the estrous cycle.

The objective of this study was to determine the relationships between follicle stimulating hormone, (FSH), estradiol (E(2)), and progesterone (P(4)) concentrations in peripheral blood samples and the follicular dynamics prior to and during superovulation in heifers pretreated with FSH-P (10 mg, i.m.) (FSH-P-primed; n=9) or not (saline-primed; n=9) on Day 3 (Day 0 = estrus) of the estrous cycle. On Day 10, all heifers were superovulated with FSH-P (27.7 mg i.m.) in declining dosages over 5 days. Prior to and during superovulation, blood samples were collected one to five times daily, and the follicular dynamics were monitored daily by ultrasonography. Prior to superovulation, profiles of P(4) and E(2) did not differ (P>1) between the saline- and FSH-P-primed heifers. The FSH concentrations in saline-primed heifers decreased from 0.43 +/- 0.05 ng/ml to 0.30 +/- 0.04 ng/ml between Days 3 and 7 and then increased progressively to 0.59 +/- 0.04 ng/ml on Day 10. In contrast (P<0.002), FSH concentrations in the FSH-P-primed heifers remained constant between Days 3 and 10 and averaged 0.41 +/- 0.03 ng/ml. Higher increases in E(2) during superovulation (maximum values, 100 vs 46 pg/ml) and in P(4) after superovulation (maximum values, 39 vs 22 ng/ml) in the saline-than in the FSH-P-primed heifers reflected the greater increase in the number of follicles (>10 mm) and in the number of corpora lutea (CL) in the saline-primed heifers. Prior to the preovulatory luteinizing hormone (LH) peak during superovulation, there was a parallel (P>0.1) decrease in FSH concentrations in the saline- and FSH-P-primed groups. Within heifers partial correlations indicated that E(2) was correlated positively with the number of follicles (>/= 7 mm) and the size of the largest follicle during superovulation (r=0.54 to 0.81; P<0.01). Negative correlations were detected (P<0.01) between FSH and the number of follicles >/=7 mm prior to (r=-0.26) and during superovulation (r=-0.37). The results cofirm earlier reports indicating that priming with FSH-P decreases the superovulatory response in cattle. Interrelationships of hormonal and ovarian responses support the concept that the presence of large dominant follicles prior to superovulation limits the superovulatory response.

Journal Article↗
PubMed2005

In vitro and in vivo viability of vitrified and non-vitrified embryos derived from eCG and FSH treatment in rabbit does.

This study aimed to evaluate the in vitro and in vivo viability of vitrified and non-vitrified embryos derived from eCG and FSH treatments in rabbit does. Ninety-six nulliparous does were randomly subjected to consecutive superovulation treatments with eCG (20 IU/kg body weight intramuscularly (i.m.), eCG group), FSH (3 x 0.6 mg/doe at 24 h intervals i.m., FSH group), or without superovulation treatment (control group). Does were artificially inseminated 3 days later and ovulation was induced immediately by hCG (75 IU/doe intravenous). Seven experimental groups were differentiated: first FSH and eCG treatment, second FSH and eCG treatment, eCG-interchanged group (does with previous FSH treatment), FSH-interchanged group (does with previous eCG treatments) and control group. Embryos were collected in vivo by laparoscopy 76-80 h post-insemination in the first and second recovery cycles and post mortem in the third recovery cycles. The ovulation rate was significantly higher in does treated with the first-FSH than in those treated with eCG or in control does (25.2+/-2.0 versus 19.2+/-1.4 to 11.0+/-1.5, and 12.2+/-1.2, first-FSH, first-eCG to second-eCG and control groups, respectively, P < 0.05). Significant differences were observed in the total recovery influenced by ovulation rate in each group (20.3+/-2.2 to 9.4+/-1.2, first-FSH to control groups). Embryo donor rate (donor with at least one normal embryo) was similar among groups with an overall of 75.1%. The number of normal embryos recovered per doe with at least one normal embryo increased significantly in relation to ovulation rate (17.7+/-2.2 to 8.41+/-3, first-FSH and control groups). The vitrification of embryos negatively affected their in vitro development to hatched blastocyst in all groups (88.1% versus 48%, P > 0.05). However, after embryo transfer, this negative effect was only observed in superovulated vitrified embryos (16.8 and 12.8% versus 39.4% total born rate from eCG, FSH and control vitrified groups, P < 0.05). Results indicated that the primary treatments with eCG or FSH increased the number of normal embryos recovered per donor doe, but these embryos are more sensitive to vitrification protocols.

Animals↗
PubMed1998

Direct actions of gonadal steroid hormones on FSH secretion and expression in the infantile female rat.

FSH-beta mRNA is dramatically regulated in the infantile female rat anterior pituitary. Elevated plasma levels of FSH correspond with increased FSH-beta mRNA levels which peak on PND 12. The source of this regulation does not appear to be GnRH, since the administration of a potent GnRH antagonist does not suppress FSH-beta mRNA levels. Consequently, we have examined the effects of the gonadal steroid hormones, estrogen and androgen, on the maintenance of gonadotropin secretion and gene expression both in vivo and in vitro. Androgen and estrogen action was blocked in vivo with the specific receptor antagonists, flutamide (150 microg) and tamoxifen (200 microg). Administration of antagonists during two different three day time-periods of infantile life [postnatal day (PND) 8-11 and PND 11-14] resulted in differing effects on both FSH and LH secretion as well as on FSH-beta and LH-beta mRNA levels. Flutamide and tamoxifen treatment both suppressed FSH secretion at either age examined (p < 0.01). LH secretion was suppressed by both treatments but only at the younger of the two ages (p < 0.01). In contrast to its effects on FSH secretion, tamoxifen suppressed FSH-beta mRNA levels in the later group only. LH-beta mRNA levels were suppressed by tamoxifen, but only in the younger age group (p < 0.05). The direct effects of steroid hormones on infantile pituitary gonadotrophs were examined in vitro by incubating cells with dihydrotestosterone propionate (DHTP; 10(-8) M) or 17beta-estradiol (E; 10(-8) M). Both DHT and E treatment stimulated FSH secretion when measured 48 h later (p < 0.01). There were no effects on LH secretion. FSH-beta mRNA levels were also stimulated by DHT at 48 h (p < 0.01). Estradiol treatment transiently increased FSH-beta mRNA levels at 2 and 6 h following treatment (p < 0.01) but not at 48 h. LH-beta levels were suppressed by DHT treatment (p < 0.05), and E transiently elevated LH-beta mRNA levels at 2 h (p < 0.05). Taken together these studies indicate that gonadotrophs from infantile female rats are capable of responding directly to steroid hormones, and may play a role in the selective stimulation of FSH secretion and expression in vivo.

Animals↗
PubMed1998

Inhibin A and inhibin B in women with polycystic ovarian syndrome during treatment with FSH to induce mono-ovulation.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is characterized by the presence of numerous small antral follicles arrested at a diameter of less than 10 mm. As development of large antral follicle(s) can be stimulated by the administration of FSH, it has been suggested that the arrest of follicle development is due to a relative lack of or resistance to FSH. We have measured the concentration of FSH and LH and the ovarian hormones oestradiol, inhibin A and B, in relation to the dynamics of follicular development in women with PCOS under basal conditions and during treatment with FSH. DESIGN: The concentrations of FSH, LH, oestradiol, inhibin A and B were measured in women with PCOS who were untreated (n = 9) or following progesterone-induced menses (10 cycles in six women) and control women on day 3 of a normal cycle (n = 10). Serial measurements of the same hormones were made during induction of ovulation with low dose of exogenous FSH in the women with PCOS who had been treated with progesterone. The dynamics of follicle development were measured by serial pelvic ultrasound examinations during treatment with FSH in PCOS and in the follicular phase of control cycles. PATIENTS: Nine anovulatory untreated women with PCOS were compared with 10 normal women and six women with PCOS undergoing FSH treatment. RESULTS: The concentrations of inhibin B and LH were higher in both groups of women with PCOS than in normal control women on day 3. In untreated women with PCOS the concentration of inhibin A was also significantly elevated compared to control women (P < 0.01) but not in women pretreated with progesterone. Basal concentrations of oestradiol were also significantly higher in women with PCOS than in the early follicular phase of the normal cycle. There were no significant differences in the concentration of FSH between the groups. Treatment of women with PCOS with low doses of FSH stimulated the development of a single dominant follicle which had an identical rate of growth and secretion of oestradiol and inhibin A to that observed in spontaneous cycles in normal women. In contrast to normal women, the concentration of inhibin B rose 7-fold following FSH treatment and remained elevated until the luteal phase. CONCLUSIONS: The raised concentrations of inhibin A and B in women with PCOS probably reflects the increased number of small antral follicles characteristically present in that condition. The striking similarity in the dynamics of growth of the dominant follicle and the pattern in concentration of oestradiol and inhibin A in normal women and in women with PCOS treated with modest amounts of FSH, suggests that the arrest of follicle development in PCOS may be due to a relative deficiency of FSH which may in turn be secondary to increased secretion of either or both inhibin forms.

Adult↗
PubMed1998

Serum inhibins A and B fall differentially as FSH rises in perimenopausal women.

BACKGROUND: Serum FSH levels rise with increasing age in normal women, particularly as they enter the menopausal transition and progress to the postmenopausal state. The contributions of decreasing levels of inhibin-A (INH-A) and inhibin-B (INH-B) to this rise are presently unclear, as there are no reports of dimeric INH levels in relation to menopausal status. The present study was undertaken in order to provide preliminary data on relationships amongst the dimeric inhibins, oestradiol (E2) and FSH in normal subjects of defined menopausal status. METHODS: Single serum samples were obtained between cycle days 3 and 8 in regularly cycling women, or at random in those with irregular cycles or amenorrhoea, in 110 women, aged 48-59 years, in the third year of a prospective longitudinal study of the menopausal transition, 'The Melbourne Women's Mid-Life Health Project'. Samples were assayed for FSH, E2, INH-A, INH-B and immunoreactive inhibin (IR-INH) and results were analysed following logarithmic transformation. Undetectable values were assigned the limit of sensitivity of the respective assays. The relationships between hormones were evaluated as a function of menopausal stage. The latter was assigned as Stage 1, premenopausal (no reported change in menstrual cycle pattern), Stage 2, early peri-menopausal (reported change in menstrual cycle frequency in the preceding year with a bleed in the preceding 3 months), Stage 3, late peri-menopausal (no menses in the preceding 3-11 months) and Stage 4, postmenopausal (no menses in the preceding 12 months). RESULTS: The hormone concentrations in premenopausal subjects (geometric means, FSH 13.5 IU/l, E2 306 pmol/l, IR-INH 217 U/l, INH-A 96 ng/l, and INH-B 48 ng/l) were used as reference points for the other stages of menopausal status. Early peri-menopausal subjects had significantly lower levels of IR-INH (147 U/l) and INH-B (13.5 ng/l) in the presence of a small, statistically nonsignificant rise in FSH (to 21.4 U/l) and no significant change in E2 or INH-A. In late peri-menopausal subjects, IR-INH fell to 76 U/l, INH-A fell to 4.2 ng/l, whilst INH-B was not significantly different at 14 ng/l. FSH had risen significantly to 72.21 U/l. Oestradiol also fell significantly to 89 pmol/l. In the postmenopausal subjects there were no further significant changes in the peptide hormones or FSH, but E2 fell further to 41 pmol/l. There was a significant (P < 0.05) inverse correlation between FSH and E2 (R = -0.78), FSH and IR-INH (R = -0.66), FSH and INH-A (R = -0.53), FSH and INH-B (R = -0.29) while IR-INH and either INH-A or INH-B were positively correlated (R = +0.57 and +0.35, respectively). The data are consistent with negative feedback roles for both dimeric inhibins and E2 as contributors to the regulation of FSH secretion as menopausal status changes. CONCLUSIONS: The major significant endocrine event in women in the early peri-menopausal phase of the menopausal transition is a substantial fall in the circulating levels of inhibin-B with no significant change in inhibin-A or oestradiol. Progression to late peri-menopausal status is accompanied by a marked fall in inhibin-A and oestradiol and a rise in FSH without further change in inhibin-B. Inhibin-B, a marker of follicle number, is a significant factor in the endocrinology of the menopausal transition.

Cross-Sectional Studies↗