Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “FSH”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 991 records · Page 55Linked to original sources
PubMed1991

Inverse effects of activin and inhibin on the synthesis and secretion of FSH and LH by ovine pituitary cells in vitro.

Little information is available on the effects of activin and inhibin on the synthesis and secretion of pituitary gonadotrophins in species other than the rat. In this in-vitro study, ovine pituitary cell cultures derived from immature sheep were used to investigate the effects of recombinant human activin-A and native Mr 32,000 bovine inhibin on basal and gonadotrophin-releasing hormone (GnRH)-induced release of FSH and LH. Residual cellular contents of FSH and LH were also determined, allowing total content/well to be calculated. Activin-A promoted a dose-dependent increase in basal (+72%; P less than 0.001) and GnRH-induced (+25%; P less than 0.001) release of FSH as well as in the residual cell content (+114%; P less than 0.001) and total FSH content/well (+67%; P less than 0.001). Conversely, inhibin significantly (P less than 0.001) suppressed each aspect of FSH production examined, confirming that in sheep, as in rats, activin and inhibin exert opposing effects on pituitary FSH production. In contrast to the rat, however, in which activin is reported to have no effect on LH secretion, exposure of sheep pituitary cells to activin-A promoted a dose-dependent suppression (-42%; P less than 0.001) of GnRH-induced LH release. This was associated with a corresponding increase (P less than 0.001) in residual cellular content of LH. Consistent with a previous report from this laboratory, inhibin had the opposite effect and significantly enhanced (+47%; P less than 0.001) GnRH-induced LH release. This was associated with a corresponding fall (P less than 0.01) in residual cellular content of LH.(ABSTRACT TRUNCATED AT 250 WORDS)

Activins↗
PubMed2004

Differential secretion of gonadotrophins: investigation of the role of secretogranin II and chromogranin A in the release of LH and FSH in LbetaT2 cells.

This study investigated the role of the secretory granule proteins, secretogranin II (SgII) and chromogranin A (CgA), in the differential secretion of FSH and LH from LbetaT2 mouse gonadotroph cells. Exogenous activin, which synergises with GnRH, is essential for the release of FSH from these cells, but also has stimulatory effects on LH and enhances GnRH-induced LH secretion. Two experiments are reported. In experiment 1, cultures were supplemented with activin (0-50 ng/ml), with and without a daily 1 h treatment of 10 nM GnRH, for 3 days. Protein secretion and mRNA levels were measured. In experiment 2, cells were treated with activin (50 ng/ml) alone, a daily 1 h treatment of 10 nM GnRH, or a combination of both for 6 days. In addition, cells exposed to activin+GnRH for 3 days were subsequently left untreated or given activin or GnRH alone for a further 3 days for comparison with cells maintained in activin+GnRH for 6 days. Protein secretion, intracellular protein and mRNA levels were measured. FSH secretion was stimulated, dose dependently, by activin and this effect increased synergistically in the presence of GnRH. The close correlation between secreted and intracellular FSH and FSHbeta mRNA levels was maintained in cells that had undergone treatment withdrawal after previous exposure to activin+GnRH, but there was no correlation between FSH and the granins. These results are consistent with the view that FSH released in response to activin/GnRH is constitutively secreted via a granin-independent pathway. SgII secretion mirrored the GnRH-induced secretion of LH, but was unaffected by activin, which stimulated LH secretion and had a detrimental effect on CgA mRNA transcription. This confirms previous observations that the LH released in response to GnRH is co-released with SgII via a regulated, granin-dependent pathway, and, in addition, suggests that activin may stimulate LH secretion through a constitutive, granin-independent pathway.

Activin Receptors↗
PubMed1985

FSH secretion in pinealectomized rams subjected to artificial photoperiods.

Eight mature Romney rams which had been pinealectomized and another eight sham-operated rams were allocated equally to one of two contrasting lighting regimes. They were housed indoors with the temperature held constant, offered a constant diet and plasma samples were collected each week for 9 months. Changes in plasma FSH in pinealectomized and sham-operated rams were similar when the rams were subjected to normal seasonal changes in photoperiod, with lower FSH levels recorded under increasing daily photoperiods than during the phase of decreasing (stimulatory) photoperiods. In contrast a reversed pattern of changes in lighting advanced the increase of plasma levels of FSH in the case of sham-operated rams, because the period of decreased daily photoperiods occurred earlier in this situation. In this case, however, pinealectomized rams did not behave like the control animals, but had raised plasma FSH levels at the same time as rams on the normal lighting regime. These results demonstrate that the pineal-mediated effects of photoperiod on reproduction in sheep directly involve FSH secretion and that seasonal cyclic changes in FSH secretion persist even after pinealectomy.

Animals↗
PubMed1986

Initiation of ovarian follicular maturation without a surge of FSH in cyclic rats treated with antiserum to LH-releasing hormone.

The relationship between a surge of FSH and the initiation of follicular maturation was examined using rats with a 4-day oestrous cycle. When antiserum against LH-releasing hormone (LHRH-AS) was given at 13.00 h on the day of pro-oestrus (day 0), surges of FSH and LH were blocked. Plasma FSH and LH were maintained at low basal levels without a surge release until the next spontaneous surge occurred on the afternoon of day 4, the predicted day of pro-oestrus. Follicular responsiveness to an injection of human chorionic gonadotrophin (hCG) indicated that preovulatory follicles, present at the time of treatment with LHRH-AS, were capable of ovulating on day 1 but had regressed by day 2. Subsequently, as shown by the ovulatory response to hCG, a new set of follicles had begun to mature by the morning of day 3 without a preceding surge of FSH. Changes in oestradiol-17 beta levels in the plasma throughout the oestrous cycle were the same in rats injected with LHRH-AS or non-immune control serum. The mature follicles in the rats treated with LHRH-AS thus retained the capacity to ovulate after losing their ability to secrete oestrogen. These results suggest that an FSH surge is not essential for initiation of follicular maturation and that basal levels of FSH may be enough to initiate follicular maturation in the absence of newly formed corpora lutea.

Animals↗
PubMed1986

Effects of constant infusion of gonadotrophin-releasing hormone in ovariectomized ewes with hypothalamo-pituitary disconnection: further evidence for differential control of LH and FSH secretion and the lack of a priming effect.

Experiments were conducted in ovariectomized ewes after hypothalamo-pituitary disconnection (HPD) to examine LH and FSH secretion during constant infusion of gonadotrophin-releasing hormone (GnRH) or physiological saline and to determine whether or not a constant GnRH background enhances or diminishes pituitary responsiveness to GnRH pulses. Whereas pulsatile GnRH infusions maintained LH and FSH secretion, constant infusions (125 or 250 ng/h) led to the complete cessation of LH secretion and reduced FSH secretion. The rate of decline of plasma FSH concentrations was significantly (P less than 0.01) greater in animals receiving 250 ng GnRH/h than in saline-treated animals, whereas that in animals receiving 125 ng/h was not significantly different. When GnRH pulses were administered during constant GnRH infusion, the plasma LH pulse amplitudes were similar to those seen without the GnRH background. These data show that, in ovariectomized-HPD ewes FSH secretion does not require GnRH pulses and may merely reflect ongoing FSH synthesis and a constant low background of GnRH does not affect pituitary responsiveness to GnRH pulses.

Animals↗
PubMed1987

Plasma patterns of LH, FSH and prolactin in rats with a polycystic ovarian condition induced by oestradiol valerate.

The patterns of plasma LH, FSH and prolactin concentrations were investigated in rats with a polycystic ovary condition (PCO). The condition was induced by treatment with oestradiol valerate 9 weeks before blood sampling. Serial blood samples were taken at 10-min intervals for 4 h from ten rats with PCO. All samples were assayed for LH, those from five animals for FSH and those from the remaining five animals for prolactin. In addition, five control animals with normal oestrous cycles were sampled during oestrus and the samples assayed for LH. Mean concentrations of LH, FSH and prolactin in rats with PCO were 140 ng/l, 76 micrograms/l and 7.6 micrograms/l respectively. All three hormones exhibited an episodic pattern. The mean peak amplitudes of LH, FSH and prolactin were 120 ng/l, 25 micrograms/l and 3.5 micrograms/l respectively. All three hormones exhibited a similar mean frequency of four or five episodes per 4 h. The LH and FSH patterns were closely synchronized; nearly all FSH peaks coincided with LH peaks. The prolactin pattern did not, however, correlate with that of the gonadotrophins. Despite the persistent oestrous condition of the animals with PCO, it was clear that their pattern of LH did not resemble that of cyclic animals in normal oestrus; in the normally cyclic animals in oestrus the pulse period was nearly twice as long and the pulse amplitude was more than sixfold greater than those in animals with PCO. We conclude that the unique episodic patterns of gonadotrophins are more important than mean blood concentrations of these hormones in establishing and maintaining the polycystic ovary syndrome.

Animals↗
PubMed1987

Intratesticular injection of glycerol as a model for studying the quantitative relationship between spermatogenic damage and serum FSH.

Intratesticular injection of glycerol (1,2,3-trihydroxypropane) was evaluated as an experimental approach for studying the relationship between spermatogenic activity, i.e. relative proportion of euspermatogenic and aspermatogenic tubules in the testis, and serum concentrations of FSH. Adult rats received a single intratesticular injection of either 400 microliters distilled water or five different doses of glycerol, ranging from 25 to 400 microliters, and were killed after 1 or 4 weeks respectively. Injection of glycerol caused focal destruction, so that the same testes contained intact tubules, tubules with spermatogonia and Sertoli cells only, and tubules devoid of cellular material. There was a close correlation (r = 0.896) between the frequency of intact tubules and the dose of glycerol, and a similarly strong correlation (r = 0.908) between acellular tubules and the dose of glycerol. A correlation existed between FSH and euspermatogenic tubules (r = -0.758, n = 122) and, conversely, between FSH and acellular tubules (r = 0.820, n = 122), while the correlation for tubules containing spermatogonia and Sertoli cells was only marginal (r = -0.055). The exact relationship between FSH and spermatogenic activity in the testis was used to estimate the minimal amount of spermatogenic tissue necessary for maintaining normal serum concentrations of FSH. Only the disruption of spermatogenesis in more than 30% of seminiferous tubules in each testis caused increased serum concentrations of FSH.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Selective release of FSH in lactating rats during the period of follicular atresia induced by the administration of antiserum to LH-releasing hormone.

Passive immunoneutralization of LHRH by injecting a caprine antiserum to LHRH (LHRH-AS) in lactating rats nursing two pups on day 5 of lactation resulted in an immediate decline in concentrations of LH in the plasma during the 24-h study period, followed by a gradual increase to control levels 30 h later. Concentrations of oestradiol-17 beta and inhibin activity in ovarian venous plasma also decreased abruptly in LHRH-AS treated animals and recovered to control levels 36 h later. These changes were correlated with changes in concentrations of LH in the plasma. On the other hand, plasma concentrations of FSH increased abruptly in the LHRH-AS treated animals within 3 h after injection, but the concentrations declined gradually to control levels 48 h later. The ability of follicles to ovulate in response to human chorionic gonadotrophin (hCG) began to decrease within 6 h after treatment with LHRH-AS, and further decreased until 18 h after injection of LHRH-AS, when hCG induced ovulation (with two oocytes) in only one of five animals. A gradual increase in ovulation rate to control levels was noted by 36 h after injection of LHRH-AS. These results indicate that Graafian follicles present at the time of LHRH-AS injection had become atretic and that a new set of follicles had then begun to mature. Selective release of FSH could not be induced by injection of LHRH-AS in ovariectomized animals. Treatment with inhibin (porcine follicular fluid) suppressed the selective release of FSH, whereas treatment with oestradiol-17 beta had no inhibitory effect on the selective release of FSH. These findings indicate (1) that tonic secretion of LH is an important factor in normal follicular maturation and maintenance in lactating rats, (2) that selective release of FSH after injection of LHRH-AS is attributed to the removal of a negative influence of inhibin from antral follicles during the period of follicular atresia and (3) that a selective surge of FSH is responsible for initiation of new follicular maturation.

Animals↗
PubMed1988

Effects of 31 kDa bovine inhibin on FSH and LH in rat pituitary cells in vitro: antagonism of gonadotrophin-releasing hormone agonists.

The effects of 31 kDa bovine inhibin on the release of FSH and LH stimulated by gonadotrophin-releasing hormone (GnRH) or its agonist analogue buserelin have been studied using 5-day-old cultures of pituitary cells prepared from adult male Sprague-Dawley rats. Exposure of cultures to increasing concentrations of inhibin for 3 days before and during a 4-h stimulation with GnRH resulted in the progressive suppression of both basal and stimulated gonadotrophin release. At the highest inhibin concentrations FSH release was abolished (inhibin median inhibitory concentration (IC50) = 0.15 U/ml) whereas LH release was suppressed by 75% (IC50 = 0.93 U/ml). To correct for the reduced size of the FSH pool resulting from inhibin pretreatment, the amount of FSH or LH released by an agonist was expressed as a proportion of the total hormone available for release in each case. Following this adjustment, concentrations of inhibin producing maximal effects increased the GnRH median effective concentration for FSH release 4.1-fold and that for LH release 2.2-fold, with inhibin IC50 values of 0.45 and 0.32 U/ml respectively. Inhibin also suppressed the maximum proportion of both FSH and LH that excess GnRH released in 4 h by 36%, with IC50 values of 0.53 and 0.76 U/ml respectively. These effects were not changed by reduction of the inhibin pretreatment period from 3 days to 1 day or by exclusion of inhibin during the stimulation period. After a 3-day pretreatment, inhibin inhibited gonadotrophin release by buserelin less effectively than that by GnRH, but the pattern of antagonism was the same.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Effects of morphine and naloxone on plasma levels of LH, FSH, prolactin and growth hormone in the immature male pig.

The effects of acute i.v. administration of gonadotrophin-releasing hormone (GnRH; 0.1 micrograms/kg), morphine (3 mg/kg) and/or naloxone (0.5 mg/kg) on LH and FSH secretion was evaluated in young male pigs (approximately 6 weeks old) with venous brachiocephalic cannulae. The effects of morphine and/or naloxone treatments on prolactin and GH were also evaluated. The influence of morphine on hypophysial hormone secretion was also examined 2 days after castration. Animals treated with morphine and/or naloxone were compared with saline-injected control animals. Injection of GnRH induced 400 and 50% increases in LH and FSH respectively. Morphine and/or naloxone did not influence LH secretion in intact or castrated animals. Morphine suppressed (P less than 0.01) FSH levels 40-60 min after injection whereas naloxone had no effect. Castration eliminated morphine-induced suppression of FSH. Injection of morphine followed by naloxone resulted in acutely raised (P less than 0.05) FSH concentrations. Morphine induced a threefold increase (P less than 0.01) in prolactin within 30 min of injection and naloxone inhibited the effect of morphine. Levels of GH were increased (P less than 0.01) 20 min after morphine treatment and this increase was delayed when naloxone was given immediately after morphine. Naloxone alone did not affect prolactin or GH secretion. Castration caused increases in LH (P less than 0.05) and FSH (P less than 0.01), did not influence prolactin or GH, and reduced plasma testosterone to undetectable (less than 1.0 nmol/l) levels. These results suggest that in young male pigs the hypothalamic-hypophysial axis is responsive to GnRH and gonadal negative feedback.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Effects of pure FSH and LH preparations on the number and function of Leydig cells in immature hypophysectomized rats.

The effects of pure FSH and/or LH preparations on the number of Leydig cells and their function in immature hypophysectomized rats have been investigated. As a result of hypophysectomy at the age of 17-18 days, the number of recognizable Leydig cells per testis decreased, as did the steroidogenic capacity in vivo and in vitro. Treatment with 64 micrograms FSH on both 22 and 23 days of age, did not affect the number of recognizable Leydig cells. In contrast, two injections of LH (10 micrograms) caused a sixfold increase in the number of Leydig cells, but had a negative effect on spermatogenesis. These stimulatory and inhibitory effects of LH diminished when FSH was added. Treatment with FSH for 7 days caused a twofold increase in the number of Leydig cells when compared with hypophysectomized controls. 3 beta-Hydroxysteroid dehydrogenase (3 beta-HSD) and esterase activity in Leydig cells also increased under the influence of FSH. The pregnenolone production per Leydig cell in the presence of 5-cholesten-3 beta,22(R)-diol (22R-hydroxycholesterol) as substrate showed a sevenfold increase. Plasma testosterone levels 2 h after injection of human chorionic gonadotrophin in intact rats and hypophysectomized FSH-treated rats were the same. Following LH treatment for 7 days, the number of Leydig cells proved to be 11 times higher, and 3 beta-HSD and esterase activity were not different from intact controls. The testicular pregnenolone production was four- to fivefold higher when compared with untreated hypophysectomized rats. However, pregnenolone production per Leydig cell in LH-treated rats was only slightly different from the hypophysectomized controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

The hypothalamus and photoperiodic control of FSH secretion by melatonin in the male Syrian hamster.

In the photoinhibited castrated male Syrian hamster, removal of the pineal gland or transfer to long photoperiods was followed by a rapid increase in the serum concentration of FSH. Levels were significantly above those of controls within 10 days. Central passive immunization of pineal-intact photoinhibited castrated animals against melatonin had a stimulatory effect on serum FSH levels, comparable with that observed following pinealectomy or transfer to short days. The effects of pinealectomy were blocked by programmed s.c. infusions of melatonin in a time-dependent manner. Serum FSH levels remained low in animals receiving 100 ng melatonin delivered over 10 h but the same mass of melatonin delivered over 4 h had no effect on the response to pinealectomy. Lesions of the anterior hypothalamus had no effect on the pinealectomy-induced increase of serum FSH in animals receiving saline infusions. However, in lesioned animals, programmed infusions of melatonin were no longer able to suppress the rise in FSH following pinealectomy. These results demonstrated that pineal melatonin is the mediator of central photoperiodic control of FSH secretion. The duration of the melatonin signal determines its effectiveness and an intact anterior hypothalamus is necessary for the signal to be read and/or the appropriate neuroendocrine response expressed.

Animals↗
PubMed1992

The role of inhibin and oestradiol in the control of FSH secretion in the sheep.

The relative importance of inhibin and oestradiol in the control of FSH and LH secretion in the ewe was investigated by passive immunization in intact animals and by hormone replacement therapy following acute ovariectomy, in the same experiment. Mature Scottish Blackface ewes on day 10 of the luteal phase were allocated to nine groups of four to five animals. Four groups were ovariectomized and immediately treated with either progesterone alone or in combination with steroid-stripped ovine follicular fluid ('inhibin') and/or oestradiol. Three further groups of ewes were left intact and injected with antibodies to the 1-26 alpha peptide fragment of porcine inhibin and/or oestradiol-17 beta. Two groups of animals were either ovariectomized alone with no further treatment, or were left intact and treated with normal sheep plasma to act as controls. Blood samples were collected at 2 h intervals from 12 h before until 48 h after ovariectomy/immunization, and from 12 to 24 h after treatment, blood samples were collected at 10-min intervals. After ovariectomy there was a large rise in the peripheral concentration of LH (P less than 0.001) which was not affected by treatment with progesterone alone but was completely prevented by treatment with progesterone and oestradiol. Treatment with inhibin had no effect on this post-castrational rise in LH. In intact ewes, immunization against oestradiol, alone or in combination with inhibin, resulted in a rise in the concentration of LH, while immunization against inhibin had no effect on LH concentration. The peripheral concentration of FSH showed a significant (P less than 0.001) increase after ovariectomy which was not affected by treatment with progesterone alone. Treatment with inhibin or oestradiol alone caused a significant (P less than 0.01) reduction in this rise, while treatment with inhibin and oestradiol together completely prevented this post-castrational rise in FSH concentration. Passive immunization against inhibin or oestradiol alone resulted in a transitory (P less than 0.01) rise in the peripheral concentration of FSH, while immunization against the two hormones in combination resulted in a significantly (P less than 0.01) larger rise. During the 14-h period after treatment, the rise in the concentration of FSH in this combined immunization group was not significantly different from that seen in the control ovariectomized group. These results provide evidence that FSH secretion is under the control of both oestradiol and inhibin, while reinforcing the hypothesis that inhibin is not involved in the regulation of LH production, which is under the dual control of oestradiol and progesterone.

Animals↗
PubMed1994

The dynamics of gonadotrophin-releasing hormone, LH and FSH secretion during the spontaneous ovulatory surge of the mare as revealed by intensive sampling of pituitary venous blood.

Conflicting views exist on the mode of gonadotrophin-releasing hormone (GnRH) secretion during the ovulatory LH surge and the relative importance of changes in pituitary responsiveness to GnRH in generating the LH surge. This disagreement may stem from species differences and/or methodological problems. To provide data on the exact relationship between GnRH and gonadotrophin secretion during the spontaneous LH surge, we collected pituitary venous (PV) blood every 30 s for 3-4 h from eight mares and then assayed GnRH (in six of the mares), FSH and LH. Jugular blood was also collected from twelve mares without PV cannulae either thrice daily during the surge (n = 8) or hourly for 24 h when close to ovulation (n = 4) and assayed for LH. Hormone peaks in PV blood were detected by the Cluster program and PV hormone patterns were scanned for underlying periodicity using spectral analysis. Jugular LH concentrations rose slowly and steadily without abrupt increase during the prolonged ovulatory surge, suggesting that hormone secretory patterns seen during the periods of rapid sampling were typical of the surge. Jugular LH concentrations were similar in mares with and without PV cannulae. Intensive sampling of PV blood showed that GnRH, FSH and LH were secreted in frequent (two to five per h) brief (5-7 min) peaks. Secretion was not detectable in 24%, 28% and 57% of the total sampling time for GnRH, LH and FSH respectively. GnRH and LH peaks appeared to be irregular in time and amplitude in most mares. However, spectral analysis of the data revealed an underlying periodicity in the secretion of all three hormones, with the dominant period ranging from 20 to 65 min in individual mares. The spectra of GnRH, FSH and LH were highly coherent at this dominant frequency, and 90% of GnRH peaks were concurrent with LH peaks, which is consistent with the dogma that GnRH is the primary secretagogue for both FSH and LH. Although PV FSH and LH concentrations were closely correlated, PV GnRH and gonadotrophin concentrations were only weakly correlated, implying that there was no consistent relationship between the magnitudes of changes in GnRH and gonadotrophin secretion. When compared with our published mid-luteal phase values, the daily GnRH secretion rate during the LH surge was trebled, while the LH responsiveness to endogenous GnRH, as assessed by the ratio between newly secreted LH and PV GnRH concentrations, was four times greater.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1996

Neonatal administration of FSH increases Sertoli cell numbers and spermatogenesis in gonadotropin-deficient (hpg) mice.

We previously demonstrated that androgens alone, in the complete absence of gonadotropins, initiated qualitatively complete spermatogenesis in hypogonadal (hpg) mice. Although germ cell to Sertoli cell ratios were normal in hpg mice with androgen-induced spermatogenesis, testicular size. Sertoli cell and germ cell numbers only reached 40% of those of non-hpg mice, and Sertoli cell numbers were unaffected by androgen treatment started at 21 days of age. We postulated that these observations were due to diminished gonadotropin-dependent. Sertoli cell proliferation during perinatal life while the Sertoli cells still exhibited normal carrying capacity for mature germ cells. In order to test this hypothesis, we examined the effects of administering androgens and gonadotropins to hpg mice during the first 2 weeks of postnatal life when Sertoli cells normally continue to proliferate. The study end-points were Sertoli and germ cell numbers in hpg mice following induction of spermatogenesis by 8 weeks treatment with 1 cm subdermal silastic testosterone implants. Newborn pups (postnatal day 0-1) were injected s.c. with recombinant human FSH (rhFSH) (0.5 IU/20 microliters) or saline once daily for 14 days, with or without a single dose of testosterone propionate (TP) (100 micrograms/20 microliters arachis oil) or human chorionic gonadotropin (hCG) (1 IU/20 microliters). Untreated hpg and phenotypically normal littermates were studied as concurrent controls. At 21 days of age, all treated weaning mice received a 1 cm silastic subdermal testosterone implant and, finally, 8 weeks after testosterone implantation, all mice were killed. As expected, qualitatively complete spermatogenesis was induced in all groups by testosterone despite undetectable circulating FSH levels. Exogenous rhFSH increased testis size by 43% (P < 0.002) but a single neonatal dose of either TP or hCG reduced the FSH effect although neither TP nor hCG had any effect alone. In contrast, a single neonatal dose of TP or hCG increased final seminal vesicle size whereas FSH had no effect. FSH and TP treatment significantly increased absolute numbers of testicular spermatids compared with saline treatment, whereas hCG and TP significantly increased testicular sperm when expressed relative to testis size. Stereological evaluation of Sertoli and germ cell numbers demonstrated a rise in the absolute numbers of Sertoli and all germ cell populations induced by neonatal administration of hormones. When expressed per Sertoli cells the numbers of germ cells in the treated mice were between 85 and 90% of non-hpg controls. We conclude that exogenous FSH treatment during the first 2 weeks of postnatal life, coinciding with the natural time of Sertoli cell proliferation, increases Sertoli cell numbers and thereby the ultimate size of the mature testis and its germ cell production. Thus neonatal gonadotropin secretion may be a critical determinant of the sperm-producing capacity of the mature testis. In addition, neonatal exposure to androgens could be important for the imprinting of sex accessory organs in hpg mice, with the long-term effects of altering the sensitivity of the accessory organs to exogenous testosterone later in life.

Animals↗
PubMed1997

Effect of the protein phosphatase inhibitor okadaic acid on FSH-induced granulosa cell steroidogenesis.

To address a possible role of type 1 and 2A serine/threonine protein phosphatases (PP1 and PP2A) in regulating granulosa cell hormonal responses, we investigated the effects of okadaic acid (OA) on FSH- and cAMP-induced steroidogenesis in these cells. When added alone (0.01-1 nmol/l), the cell-permeant phosphatase inhibitor did not affect progesterone and 3 beta-hydroxysteroid dehydrogenase/delta 5-4 isomerase (3 beta-HSD) enzyme activity, whereas when added with FSH it dose-dependently augmented (minimal effective dose, 0.1 nmol/l) gonadotropin-stimulated steroidogenesis in cultured granulosa cells. A similar stimulatory effect of the toxin was observed in cells cultured for 48 h with the cell-permeant analogue dibutyryl cAMP (1 mmol/l), or when granulosa cells were stimulated with the cAMP-inducing agents cholera toxin (1 microgram/ml), forskolin (15 mumol/l) or 1-methyl-3-isobutyl-xanthine (0.1 mmol/l). The observed effect of OA on FSH-supported granulosa cell steroidogenesis was not a consequence of increased cAMP generation, and time course experiments also revealed that a minimal time period of 12 h was necessary for OA (0.1 and 1 nmol/l) to significantly enhance FSH-induced progesterone and 3 beta-HSD enzyme activity. Since OA also inhibits the dephosphorylation of protein kinase C (PKC) substrates, we also compared the effect of OA and the PKC activator 12-O-tetradecanoylphorbol-13-acetate (TPA) on FSH-induced granulosa cell steroidogenic activity. While activation of the PKC pathway with the tumor promoter TPA (10 nmol/l) inhibited progesterone and cAMP accumulation in FSH-stimulated granulosa cells, treatment with OA augmented steroidogenesis and did not affect gonadotropin-induced cAMP generation. Collectively these results suggest that PP1 and PP2A may be important in regulating the phosphorylation state of proteins implicated in the cAMP-protein kinase A-stimulated steroidogenic activity of these cells.

1-Methyl-3-isobutylxanthine↗
PubMed1997

In vitro fertilizing capacity of sperm from FSH-treated photoinhibited Djungarian hamsters (Phodopus sungorus).

In hypogonadal male Djungarian hamsters FSH alone can induce normal spermatogenesis. However, for the induction of mating behavior, supplementation with testosterone is necessary. We have here investigated, by in vitro fertilization, whether sperm produced by photoinhibited hamsters treated with FSH alone can fertilize without testosterone. Photoinhibited hypogonadal male Djungarian hamsters were injected daily with human FSH (10 IU; Fertinorm) for 5-7 weeks. The hormone stimulated regrowth of the testes. Neither body weight nor the weights of the androgen-dependent organs-epididymides, prostates, accessory glands-showed significant differences from photoinhibited controls; furthermore FSH treatment did not raise intratesticular or serum testosterone levels. In eleven out of the twelve FSH-treated photoinhibited hamsters, elongated spermatids were found in the testes; in five out of nine epididymides, sperm was found by histological examination. In two out of the twelve FSH-treated hamsters, the amount of sperm in the caudal part of the epididymis was sufficient for in vitro fertilization with oocytes collected from superstimulated females. These spermatozoa fertilized 16-29% of the oocytes. Spermatozoa from photostimulated controls produced similar levels of fertilization.

Animals↗
PubMed2003

Differential regulation of rat testicular 5alpha-reductase type 1 and 2 isoforms by testosterone and FSH.

Testosterone is metabolised to the more potent androgen, dihydrotestosterone, by the 5alpha-reductase (5alphaR) enzyme. We previously showed that 5alpha-reduced androgens are important for maintaining androgen action on rat spermatogenesis when testicular testosterone concentrations are reduced. This study investigated expression and activity of the 5alphaR isoforms, type 1 (5alphaR-1) and type 2 (5alphaR-2), in the rat during hormone manipulation in order to understand the factors that regulate the testicular concentration of 5alphaR and testicular 5alpha-reduced androgen biosynthesis. Testicular 5alphaR-1 and 5alphaR-2 mRNA and enzyme activity were measured by real-time PCR and specific enzyme assays respectively. Hormone levels were first suppressed using two models of gonadotrophin suppression: testosterone and oestradiol treatment (LH/testosterone deficiency) or GnRH immunisation (LH/testosterone and FSH deficiency). Hormones were then either restored or suppressed for 6 days by a variety of hormonal treatments. 5alphaR-1 mRNA and enzyme activity increased when testosterone was suppressed, yet restoration of testosterone decreased 5alphaR-1 mRNA and enzyme activity, suggesting that testosterone negatively regulates 5alphaR-1. suppression of FSH decreased 5alphaR-1 mRNA yet FSH administration increased 5alphaR-1 mRNA, but no changes in 5alphaR-1 activity were observed within the 6 day period. In contrast to 5alphaR-1, testosterone did not affect the testicular concentration of 5alphaR-2 mRNA or activity, but there was evidence for modulation of 5alphaR-2 activity by FSH. Measurement of testicular androgens revealed that 5alphaR-1 was primarily responsible for the production of 5alpha-reduced metabolites. It is concluded that the 5alphaR isoforms in rat testis are differentially regulated by testosterone and FSH: testosterone negatively regulated 5alphaR-1 mRNA and enzyme activity but had no affect on 5alphaR-2, whereas FSH positively regulated 5alphaR-1 mRNA and appeared to regulate 5alphaR-2.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗