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PubMed1989

LH, FSH and ovulation rate in ewes treated with exogenous oestradiol.

In two experiments, mature Merino ewes were fitted with subcutaneous implants containing oestradiol-17 beta or empty implants (control). Peripheral concentrations of LH and FSH were measured during luteal and follicular phases, which were synchronized by means of intravaginal progestagen-impregnated sponges. The ovulation rates of the ewes were determined by laparoscopy, 1 week after luteolysis. In Exp. 1, small implants (3 mm) decreased the LH pulse frequency before luteolysis. In the ewes with oestradiol implants, the amplitude of the preovulatory surge of LH was reduced and the onsets of the LH and FSH surges were delayed. There was no effect of oestradiol on LH baseline, LH pulse amplitude or in the concentration of FSH during the luteal or follicular phases. In Exp. 2, larger implants (10 mm) were inserted for the luteal, follicular, or luteal + follicular phases. The control ewes had empty implants. In the ewes with oestradiol implants, LH pulse frequencies were decreased during the luteal phase. This decrease persisted throughout the follicular phase, even though the oestradiol implants had been removed. There were no differences in the other measures of LH or FSH in the luteal or follicular phases. Ovulation rates were not affected by oestradiol treatment in either experiment, indicating that the regulation of LH pulse frequency is not a critical factor in the determination of ovulation rate in ewes. This was supported by retrospective analysis of the gonadotrophin profiles of single and twin-ovulating ewes, in which all measures of LH were similar between the two groups. However, twin-bearing ewes had slightly higher circulating concentrations of FSH during the luteal phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Age-dependent changes in the in-vitro response of a pig Sertoli cell-enriched population to FSH.

The response of pig Sertoli cell-enriched cultures to FSH was investigated by measuring plasminogen activator (PA) secretion in culture, throughout the nonpubertal and prepubertal periods. Sertoli cell-enriched populations could be isolated from birth until a testicular weight of 56 g. FSH elicited a dose-dependent increase in PA secretion by pig Sertoli cell-enriched cultures. The ED50 was minimal for cells coming from testes weighing 10-22 g, and increased more than 2-fold for cells from heavier testes. This suggests that, at the end of the non-pubertal period, an increased FSH sensitivity is important for initiation of spermatogenesis in this species, and that during the prepubertal period Sertoli cells become less sensitive to FSH. The FSH-stimulated PA secretion increased about 10-fold from a testicular weight of 25 g onwards, i.e. when primary spermatocytes appear in seminiferous tubules.

Animals↗
PubMed1990

Acute suppression of FSH secretion by oestradiol in the ovariectomized rhesus monkey.

Using long-term ovariectomized rhesus monkeys, we examined the ability of oestradiol to decrease circulating FSH concentrations in the absence of other ovarian factors. Daily blood samples were obtained from untreated monkeys for 8 days, followed by insertion of oestradiol capsules after the Day-8 sample was taken. Samples were then taken on Days 9-15, the capsules were removed after the Day-15 sample, and samples were obtained on Days 16-19. Serum was assayed for concentration of oestradiol, FSH and LH by RIA. The concentration of FSH (ng/ml) in serum did not change during the first 8 days before oestradiol treatment (overall mean = 356 +/- 55) but decreased from the Day-8 value of 320 +/- 8 to 190 +/- 42 on Day 9 and by Day 15, after 7 days of oestradiol treatment, had reached a nadir of 20 +/- 5. By Day 17, i.e. 2 days after removal of the oestradiol capsules, serum FSH had increased (P less than 0.05) to 92 +/- 23 with a further increase (P less than 0.05) on Day 19 (171 +/- 16). This study demonstrates that, unlike in rats, mice, and sheep, administration of oestradiol alone to ovariectomized rhesus monkeys reduces immunoreactive serum FSH to concentrations measured in intact animals.

Animals↗
PubMed1990

Seasonal cycles in the blood plasma concentration of FSH, inhibin and testosterone, and testicular size in rams of wild, feral and domesticated breeds of sheep.

Seasonal cycles in testicular activity in rams were monitored in groups of wild (mouflon), feral (Soay) and domesticated breeds of sheep (Shetland, Blackface, Herdwick, Norfolk, Wiltshire, Portland and Merino) living outdoors near Edinburgh (56 degrees N). The changes in the blood plasma concentrations of FSH, inhibin and testosterone, and the diameter of the testis were measured every half calendar month from 1 to 3 years of age. There were significant differences between breeds in the magnitude and timing of the seasonal reproductive cycle. In the mouflon rams, the seasonal changes were very pronounced with a 6-15-fold increase in the plasma concentrations of FSH, inhibin and testosterone from summer to autumn, and a late peak in testicular diameter in October. In the Soay rams and most of the domesticated breeds, the seasonal increase in the reproductive hormones occurred 1-2 months earlier with the peak in testicular size in September or October. In the two southern breeds (Portland and Merino), the early onset of testicular activity was more extreme with the seasonal maximum in August. In cross-bred rams, produced by mating Soay ewes (highly seasonal breed) with Portland or Merino rams (less seasonal breeds), there was a seasonal reproductive cycle that was intermediate compared to that of the parents. A comparison between all 11 breeds showed a significant correlation between the timing of the seasonal cycle in plasma FSH concentration and testicular diameter (time of peak FSH vs testis, r = 0.95). The overall results in the rams are consistent with a primary role of FSH in dictating the seasonal cycle in testicular size and the secretion of inhibin. The earlier seasonal onset in the testicular cycle in the southern breeds of domesticated sheep, and the differences from the wild type, are taken to represent the effects of genetic selection for a longer mating season.

Animals↗
PubMed1990

Inhibin secretion after treatment with an LHRH agonist and subsequent ovarian hyperstimulation induced by FSH in the macaque (Macaca arctoides).

The effect of ovarian hyperstimulation with 'pure' FSH on serum concentrations of immunoreactive inhibin in macaques in which endogenous gonadotrophin secretion and ovarian activity had been suppressed by an LHRH agonist implant was studied. Four stump-tailed macaques were treated with an LHRH agonist implant in the early follicular phase of the cycle. After a transient stimulatory phase oestradiol secretion was markedly suppressed, and the rises in progesterone and inhibin observed after ovulation were absent. At 8 weeks after implant administration, when serum LH was only just detectable, FSH (Metrodin) was administered to the LHRH agonist-treated macaques once daily for 9 days (75 i.u. on Day 0, 35 i.u. Days 1-8). FSH treatment stimulated a marked increase in oestradiol and immunoreactive inhibin secretion in the absence of a rise in serum progesterone concentrations. Comparison of the FSH-induced pattern of inhibin secretion with the profile during the normal menstrual cycle showed that during the normal cycle inhibin is secreted into the peripheral blood almost exclusively during the luteal phase in the macaque, but stimulation of follicular development by exogenous FSH was associated with a rise in inhibin concentrations in the absence of ovulation. These results suggest that this non-physiological rise in inhibin may be one of the factors involved in the changes in endogenous gonadotrophin secretion which can occur during ovarian hyperstimulation.

Animals↗
PubMed1990

Suppression of the secondary FSH surge with bovine follicular fluid is associated with delayed ovarian follicular development in heifers.

Holstein heifers were given 5 injections (twice/day) of 10 ml charcoal-extracted bovine follicular fluid (bFF; N = 6) or 10 ml saline (N = 5) beginning 12 h after the onset of oestrus. Blood samples were collected for determination of plasma concentrations of FSH, LH, progesterone and oestradiol-17 beta. Treatment with bFF suppressed the secondary FSH surge (P less than 0.01). Cessation of bFF injections was followed by a rebound period during which FSH was elevated compared with controls (P less than 0.01). Daily ultrasonographic examinations revealed that follicular growth occurred in waves, with 4 of 5 control heifers exhibiting 3 waves and the other 2 waves. In contrast, 5 of 6 bFF-treated animals exhibited 2 waves and the other 3 waves. Appearance of follicles in the first wave was delayed in bFF-treated heifers (Day 3.3 +/- 0.3 compared with Day 1.4 +/- 0.2; P less than 0.0001) and appearance of the dominant follicle of the first wave was delayed (Day 4.5 +/- 0.3 compared with Day 1.8 +/- 0.2; P less than 0.0001). Follicles in the second wave appeared later in animals treated with bFF (Day 12.7 +/- 0.4 compared with Day 10.4 +/- 0.6; P less than 0.01), and the dominant follicle of this wave also appeared later (Day 13.0 +/- 0.5 compared with Day 10.6 +/- 0.5; P less than 0.01). Oestradiol-17 beta increased during the early luteal phase, but this increase occurred later in heifers treated with bFF (peak concentrations on Day 6.3 +/- 0.6 compared with Day 4.2 +/- 0.2; P less than 0.05). LH, progesterone and cycle length were not affected by bFF. Delayed follicular growth associated with suppression of FSH suggests that the secondary FSH surge is important in the initiation of follicular development early in the bovine oestrous cycle, and thus may play a role in the regulation of ovarian follicular dynamics.

Animals↗
PubMed1991

Effect of FSH on ovarian inhibin secretion in anoestrous ewes.

In Exp. 1, 7 Finn-Merino ewes which had one ovary autotransplanted to a site in the neck had jugular and timed ovarian venous blood samples collected at 10-min intervals for 2 h before and 3 h after injection of 5 micrograms NIAMDD-oFSH-S16. In Exp. 2, 8 Finn-Merino ewes with ovarian autotransplants had jugular and timed ovarian venous blood samples collected at 15-min intervals for 2 h before and 12 h after bolus injection of 40 micrograms NIAMDD-oFSH-S16 and infusion of oFSH-S16 at 6 micrograms/min for 4 h. In Exp. 2 the follicular population of the ovary was assessed by real-time ultrasound at the beginning and end of the experimental period. In both experiments the secretion rates of inhibin (1-3 ng/min) and oestradiol (0.5-8 ng/min) were similar to those observed during the luteal phase of the cycle in the breeding season, indicating significant follicular development in these animals. In Exp. 1 there was no change in the secretion of oestradiol or inhibin after the injection of FSH which resulted in a 25% increase (P less than 0.05) in the concentration of FSH in plasma. Inhibin secretion was pulsatile but there was no difference in inhibin pulse frequency before (1.6 +/- 0.2 pulses/h) or after (1.2 +/- 0.5 pulses/h) injection of FSH. In Exp. 2 injection of FSH resulted in an increase (P less than 0.001) in plasma concentrations of FSH in the sample taken 10 min after injection from a baseline of 1.2 +/- 0.2 ng/ml to a peak of 10.6 +/- 1.0 ng/ml (mean +/- s.e.m.).(ABSTRACT TRUNCATED AT 250 WORDS)

Anestrus↗
PubMed1993

Seasonal patterns of basal and GnRH-induced LH, FSH and testosterone secretion in Eld's deer stags (Cervus eldi thamin).

Plasma LH, FSH and testosterone were measured in blood samples collected via remote catheterization from six adult Eld's deer stags every 10 min for 8 h before and 2 h after GnRH (1 microgram kg-1, i.v.) administration. Blood samples were collected within 2 weeks of the summer solstice (21 June), autumn equinox (22 September), winter solstice (21 December) and spring equinox (20 March). Marked seasonal variations in basal LH, FSH and testosterone concentrations were observed. From autumn, well-defined LH pulses were temporally associated with small, but detectable pulses in testosterone. During the winter transition into the breeding season, episodic LH pulses were also temporally associated with corresponding testosterone surges that lasted 2-3 h. High amplitude, low frequency testosterone surges were also observed during the spring, but often in the absence of detectable LH pulses. Basal LH and testosterone concentrations decreased during the summer and, although LH pulses were detected, associated testosterone pulses were absent. Only 37% of LH pulses occurred coincidentally with FSH pulses, and FSH pulses were generally less prominent. The increases in LH and FSH above basal concentrations after GnRH treatment were significant (P < 0.05) for all seasons. Increases in testosterone after GnRH treatment were greatest during the winter and spring, but testosterone also increased to a lesser extent during the autumn (P < 0.05). In contrast, testosterone concentrations were not different before and after GnRH treatment during summer.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Differential effects of adrenalectomy on the prolactin-induced suppression of LH and FSH secretion after castration in male rats.

Hyperprolactinaemia inhibits gonadotrophin secretion in males and females of many species. The aim of this study was to determine the role of the adrenal gland in mediating the inhibitory effects of prolactin by contrasting the effects of acute hyperprolactinaemia on LH and FSH secretion in adrenal-intact and adrenalectomized rats with and without physiological corticosterone replacement. Adult male rats were administered purified ovine prolactin every 12 h (2.4 mg per injection s.c.) beginning at the time of castration. Blood samples were collected every 3 h for 36 h, then every 12 h until 10 days after castration. Ovine prolactin significantly reduced LH secretion in all groups from approximately 15 to 48 h after castration. In contrast, plasma FSH concentrations were reduced by ovine prolactin from 21 to 48 h only in the adrenal-intact rats and not in the adrenalectomized or adrenalectomized plus corticosterone groups. In all groups, ovine prolactin inhibited endogenous prolactin secretion in rats by short-loop autofeedback as soon as 3 h after the first ovine prolactin injection and throughout the 10 days of the study. Adrenalectomy per se, with or without corticosterone replacement, also had a differential effect on LH and FSH secretion after castration, causing only a transient delay in the rise in LH after castration, but inducing a significant and long-lasting inhibition of FSH secretion. The results demonstrate that ovine prolactin-induced suppression of LH secretion after castration occurs with or without the adrenal glands. Suppression of FSH secretion after castration by ovine prolactin, however, may involve an adrenal component.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed2006

Control of oestradiol secretion and of cytochrome P450 aromatase messenger ribonucleic acid accumulation by FSH involves different intracellular pathways in oestrogenic bovine granulosa cells in vitro.

The objective of this study was to determine the major intracellular signalling pathways used by FSH and insulin to stimulate cytochrome P450 aromatase (Cyp19) mRNA and oestradiol accumulation in oestrogenic bovine granulosa cells in vitro. Bovine granulosa cells from small follicles (2-4 mm diameter) were cultured for 6 days under non-luteinizing conditions in the presence of insulin at 100 ng/ml, or insulin (10 ng/ml) and FSH (1 ng/ml). On day 4 of culture, specific inhibitors of phosphatidylinositol 3-kinase (PI3K; LY-294002), protein kinase C (PKC; GF-109203X), protein kinase A (PKA; H-89) or mitogen-activated protein (MAP) kinase activation (PD-98059) were added. The addition of PI3K and PKC inhibitors, but not of PKA inhibitor, significantly decreased insulin-stimulated Cyp19 mRNA levels and oestradiol accumulation (P < 0.001). The PKA inhibitor significantly decreased FSH-stimulated Cyp19 mRNA abundance and oestradiol secretion, whereas PI3K and PKC inhibitors decreased oestradiol secretion without affecting Cyp19 mRNA accumulation. Inhibition of MAP kinase pathway significantly increased Cyp19 mRNA abundance in insulin- and FSH-stimulated cells. P450scc mRNA levels and progesterone secretion were not affected by any inhibitor in either experiment. Although FSH stimulates Cyp19 expression predominantly through PKA, oestradiol secretion is altered by PI3K and PKC pathways independently of Cyp19 mRNA levels. In addition, we suggest that Cyp19 is under tonic inhibition mediated through a MAP kinase pathway.

Animals↗
PubMed1997

Effect of FSH and insulin on lipogenesis in cultures of Sertoli cells from immature rats.

Follicle-stimulating hormone (FSH) and insulin regulate glycide metabolism in Sertoli cells, thus stimulating lactate production. These stimulatory effects of FSH and insulin do not require protein synthesis, suggesting a modulation of enzyme activity and/or regulation of glucose transport. The present investigation was performed to characterize the hormonal control of lipid metabolism in Sertoli cells. The data indicate that FSH and insulin have a regulatory effect on lipid metabolism in Sertoli cells. After 8 h of preincubation with insulin (5 micrograms/ml), the activity of the enzyme ATP-citrate lyase in cultured Sertoli cells was increased from 0.19 to 0.34 nmol NAD+ formed microgram protein-1 min-1. FSH (100 ng/ml) had no effect on this enzyme. Glycerol phosphate dehydrogenase activity was not affected by any of the hormones tested. When Sertoli cells from 19-day old rats were incubated with [1,2-14C]acetate for 90 or 360 min, the [14C] label was present predominantly in triglyceride and phospholipid fractions with minor amounts in other lipids. In Sertoli cells pretreated for 16 h with insulin and FSH, an increase in acetate incorporation into lipids was observed. Most of the label was in esterified lipids and this percentage increased with the time of treatment; this increase was remarkable in triglycerides of control cells (18.8% to 30.6%). Since Sertoli cell triglycerides participate in the control of spermatogenesis, the present data suggest that the hormonal control of lipid metabolism in Sertoli cells is important not only for maintaining the energy of the cell itself, but also for the control of the spermatogenesis process.

ATP Citrate (pro-S)-Lyase↗
PubMed1986

Testosterone maintains pituitary and serum FSH and spermatogenesis in gonadotrophin-releasing hormone antagonist-suppressed rats.

Groups of adult male rats were treated continuously for 30 days with either vehicle or the potent gonadotrophin-releasing hormone (GnRH) antagonist. (N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Trp3,D-hArg(Et2)6,D-Ala10 )- GnRH (RS 68439; 35 micrograms/day). In addition, groups of vehicle- and antagonist-treated rats received s.c. testosterone implants sufficient to maintain serum testosterone concentrations 3.5- to 5-fold higher than those of vehicle-treated control rats. After 30 days of antagonist treatment serum LH, FSH and testosterone concentrations were at or below the detection limits of their respective assays and pituitary FSH content and GnRH receptor binding were reduced, relative to control animals, by 77 and 98% respectively. Testis weight in antagonist-treated rats was reduced by 75% and spermatogenesis was suppressed to an extent comparable to that observed in hypophysectomized rats. Testosterone, which caused a 40% reduction in serum FSH relative to control animals, prevented the antagonist-induced fall in both serum and pituitary FSH, but not GnRH receptors, below that observed in the vehicle plus testosterone-treated group. Furthermore, spermatogenesis in the antagonist plus testosterone-treated group was indistinguishable from that observed in control animals. It is concluded that testosterone is capable of maintaining serum and pituitary FSH levels in vivo, under conditions which presumably render the pituitary insensitive to hypothalamic GnRH.

Animals↗
PubMed1986

Induction of ovulation during anoestrus in two breeds of sheep with multiple injections of LH alone or in combination with FSH.

The gonadotrophic requirements for the induction of ovulation and formation of a viable corpus luteum in two breeds of seasonally anoestrous sheep of differing fecundity was investigated. Welsh Mountain (n = 20) and Damline ewes (n = 19) were given LH or FSH either alone or in combination. Luteinizing hormone was injected i.v. at an increasing frequency for 72 h (one injection every 3 h for 24 h, one every 2 h for 24 h, and one every hour for 24 h) and FSH was injected in an identical manner for the first 36 h of treatment. Exogenous LH alone and in combination with FSH induced a preovulatory LH surge in all 19 ewes and ovulation in 18 out of 19 ewes of both breeds. However exogenous FSH alone was ineffective. The incidence of normal corpus luteum function in ewes induced to ovulate was low and not related to treatment, timing or magnitude of the LH/FSH surge. It is concluded that in both breeds studied it is the infrequency of LH pulses which limits the development of preovulatory follicles during seasonal anoestrus, that the requirement for FSH remains unknown, and that the induction of inadequate corpora lutea during seasonal anoestrus reflects either defects in hormonal priming of the preovulatory follicle and/or inappropriate luteotrophic support after ovulation.

Anestrus↗
PubMed1989

Passively immunizing ewes against inhibin during the luteal phase of the oestrous cycle raises the plasma concentration of FSH.

Passive immunization was used to investigate the importance of inhibin in the negative feedback loop regulating the production of FSH in sheep. An anti-serum raised to the 1-26 peptide fragment of the N-terminus of the alpha-chain of porcine inhibin was first shown to neutralize the suppressive effects of inhibin on the production of FSH by dispersed ovine pituitary cells in vitro. Groups of five mature Scottish Blackface ewes on day 8 of the luteal phase of the oestrous cycle were then injected with either 10 ml plasma from normal ewes (control) or 10 ml ovine inhibin antiserum. On day 10, luteal regression was induced by an i.m. injection of cloprostenol (100 micrograms), and ovulation rate determined 6 days later by laparoscopy. Peripheral plasma samples were collected throughout the experimental period. Following treatment, there was no change in the peripheral plasma concentration of LH in either group. Following injection of the inhibin antiserum, the concentration of FSH rose significantly (P less than 0.001) compared with the control group. The concentration of FSH rose from 1.42 +/- 0.06 to a maximum of 2.58 +/- 0.23 (S.E.M.) micrograms/l by 5.6 +/- 0.9 h, this maximum lasting 9.0 +/- 1.1 h. By 32.8 +/- 6.9 h, the concentration of FSH had returned to pretreatment levels, while the titre of free antibody in the plasma of treated ewes was still high. In the treated ewes, there were one single and four double ovulations compared with three single and two double ovulations in the control group, indicating that the inhibin immunization may have resulted in an increase in ovulation rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Evidence for temporal coupling of growth hormone, prolactin, LH and FSH pulsatility overnight during normal puberty.

The patterns of secretion of GH, LH, FSH and prolactin were determined over a single night (20.00-08.00 h; 15-min sampling) in 34 normal subjects (17 male, 17 female, aged 9.1-20.9 years). Plasma GH was measured by an immunoradiometric assay and LH, FSH and prolactin by radioimmunoassay in all samples. Data were analysed by Fourier transformation and cross-correlation after stationarization. The highest mean GH levels were noted in girls at Tanner stage 2/3 and in boys at stages 4/5. Prolactin levels were highest in girls at stage 4/5 and in boys at stage 2/3. LH and FSH showed a progressive rise by puberty stage in both sexes. The dominant pulse periodicities of GH and prolactin were 150-180 min in girls and 180 min in boys. LH and FSH pulse periodicity was around 90 min in early puberty and 180 min in later puberty in both sexes. LH and prolactin pulses showed a phase relationship with GH with a lag of 30-75 min (r = 0.32; P less than 0.001) and 30 min (r = 0.47; P less than 0.0001) respectively. Generally, LH and prolactin pulses were in phase (r = 0.42; P less than 0.0001) and there was a highly significant correlation (r = 0.64; P less than 0.0001) between FSH and LH pulsatility. Whereas mean overnight concentrations and pulse periodicity of the principal pituitary hormones varied between the sexes during early puberty, by the end of puberty a dominant pulse periodicity of around 150-180 min was established and there was remarkable temporal coupling of pulsatility.

Adolescent↗
PubMed1992

Antiprogesterone RU486 increases serum immunoreactive inhibin levels and LH:FSH and testosterone:oestradiol ratios in cyclic rats.

Since administration of the antiprogesterone RU486 to cyclic rats results in a dissociation of basal LH and FSH secretion we studied its effects on peripheral levels of inhibin, oestradiol and testosterone throughout the oestrous cycle. Cyclic rats were given RU486 (2 mg) twice daily (09.00 and 17.00 h) on metoestrus, dioestrus and pro-oestrus. Oil-treated rats were used as controls. Serum concentrations of immunoreactive inhibin in oil-treated rats increased from metoestrus to pro-oestrus and decreased at oestrus. RU486-treated rats had serum inhibin concentrations significantly increased over oil-treated rats at dioestrus and pro-oestrus, but not at oestrus. At both pro-oestrus and oestrus serum concentrations of LH, testosterone and oestradiol were significantly raised in RU486-treated rats compared with oil-treated controls. In contrast, serum FSH concentrations in RU486-treated rats were decreased on both days. Ovaries from RU486-treated rats showed an increased testosterone content at pro-oestrus, mainly in the interstitial tissue. The results of the present study demonstrate that RU486 has a stimulatory effect on inhibin secretion, and offer an explanation for the decrease in basal serum FSH levels. The low FSH secretion on the morning of oestrus in spite of the low levels of inhibin suggests that progesterone is involved in FSH secretion at this time.

Animals↗
PubMed1993

Differential regulation of FSH and inhibin gene expression and synthesis by testosterone in immature and mature male rats.

Direct effects of testosterone on gonadotrophins at the pituitary level were studied in intact and castrated immature (age 10 days) and mature (70 days) male rats. Gonadotrophin-releasing hormone action was blocked by treatment with a potent GnRH antagonist, Ac-D-pClPhe-D-pClPhe-D-Trp-Ser-Tyr-D-Arg-Leu-Arg-Pro-D-Ala-+ ++NH2CH3COOH (Ant; Organon 30276; 1.0 mg/kg body weight per day) injected subcutaneously. Silicone elastomer capsules were used for the testosterone treatment. Both treatments commenced on the day of orchiectomy and lasted for 7 days. In adult male rats Ant treatment suppressed serum testosterone from 9.5 +/- 2.5 (S.E.M.) nmol/l to below the limit of detection (< 0.10 nmol/l; P < 0.01), and the testosterone implants reversed the decrease. Treatment with Ant decreased the pituitary content of FSH-beta subunit mRNA in intact and orchiectomized rats to 14% of their respective controls (P < 0.01). These levels were increased to 80-81% of controls (not significant) in both groups by combined treatment with testosterone and Ant. Orchiectomy alone increased FSH-beta subunit mRNA by 202% (P < 0.01). In intact immature rats Ant treatment decreased the level of pituitary FSH-beta subunit mRNA to 21% (P < 0.01), and a partial recovery (P < 0.01) to 42% of controls was observed with combined Ant+testosterone treatment. In contrast, in orchiectomized immature rats, where ANT decreased FSH-beta subunit levels to 48% of controls (P < 0.01), testosterone was able to reverse these mRNA levels completely (114% of controls). No evidence for the direct pituitary effects of testosterone were found in the mRNA of the common alpha or LH-beta subunits. In adult rats, the testicular inhibin alpha and beta A subunit mRNA levels were increased (P < 0.01) by Ant+testosterone compared with Ant-treated animals, but there were no differences in serum immunoreactive inhibin between any of the uncastrated adult groups. In intact immature rats, Ant+testosterone treatment increased (P < 0.01) inhibin beta A subunit mRNA levels compared with controls and Ant-treated animals. Ant decreased the level fo peripheral inhibin immunoreactivity from 8.3 +/- 2.0 U/ml to 2.1 +/- 0.4 U/ml (P < 0.01) and testosterone reversed it to 5.8 +/- 0.6 U/ml (not significant). In conclusion, our observations indicated that testosterone is able to stimulate FSH gene expression and secretion directly in immature and adult rats, but the testosterone response is enhanced at both ages by orchiectomy, even more so in the immature rat.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Effects of FSH and testosterone on intratesticular insulin-like growth factor-I and specific germ cell populations in rats treated with gonadotrophin-releasing hormone antagonist.

Evidence derived predominantly from a series of in-vitro studies indicates that insulin-like growth factor-I (IGF-I) plays an important role as a paracrine and autocrine regulator within the testis. We investigated the effects of FSH substitution on spermatogenesis and testicular IGF-I content in rats treated with gonadotrophin-releasing hormone (GnRH) antagonist (ANT) and injected with ethane dimethane sulphonate (EDS), a Leydig cell toxin. FSH treatment partially prevented the marked decrease in intratesticular IGF-I in rats treated with only GnRH antagonist but not in GnRH antagonist+EDS-treated animals (controls, 191.0 +/- 4.5; ANT, 80.1 +/- 5.6; ANT+EDS, 81.6 +/- 3.4; ANT+EDS+FSH, 86.3 +/- 1.4; ANT+FSH, 137.7 + 7.3 (S.E.M.) ng/testis). Correlation analysis of testicular IGF-I content with the number of pachytene spermatocytes and round spermatids per cross-section revealed r values of 0.77 and 0.74 respectively (P < 0.001). We then analysed the same parameters in GnRH antagonist-treated rats which, in addition, received daily injections of the anti-androgen flutamide, in order to investigate the potential role of testosterone, as opposed to other Leydig cell products, in the regulation of spermatogenesis and testicular IGF-I. FSH treatment prevented regression of spermatogenesis in rats treated with GnRH antagonist alone but not in GnRH antagonist- and flutamide-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗