Human Recombinant Inhibin a Suppresses Plasma Follicle-Stimulating Hormone to Intact Levels but has No Effect on Luteinizing Hormone in Castrated Rams1

Tilbrook, AJ; Kretser, David M de; Clarke, I. J.

doi:10.1095/biolreprod49.4.779

Cited by 40 publications

(18 citation statements)

References 44 publications

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“…The most compelling evidence that inhibin is an important feedback regulator of FSH secretion in male ungulates has come from experiments in which castrated rams have been administered human recombinant inhibin (hr-inhibin) A. In particular, when castrated rams were infused for 12 h with a dose of hr-inhibin A that resulted in the plasma inhibin concentrations found in intact rams, the plasma concentrations of FSH were reduced to values similar to those found in intact rams [89]. This result was achieved without any effect on LH secretion [89].…”

Section: Regulation Of Fsh Secretion By Inhibinmentioning

confidence: 99%

Negative Feedback Regulation of the Secretion and Actions of Gonadotropin-Releasing Hormone in Males

Tilbrook

Clarke

2001

Biology of Reproduction

144

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This minireview considers the state of knowledge regarding the interactions of testicular hormones to regulate the secretion and actions of GnRH in males, with special focus on research conducted in rams and male rhesus monkeys. In these two species, LH secretion is under the negative feedback regulation of testicular steroids that act predominantly within the central nervous system to suppress GnRH secretion. The extent to which these actions of testicular steroids result from the direct actions of testosterone or its primary metabolites, estradiol or dihydrotestosterone, is unclear. Because GnRH neurons do not contain steroid receptors, the testicular steroids must influence GnRH neurons via afferent neurons, which are largely undefined. The feedback regulation of FSH is controlled by inhibin acting directly at the pituitary gland. In male rhesus monkeys, the feedback regulation of FSH secretion is accounted for totally by the physiologically relevant form of inhibin, which appears to be inhibin B. In rams, the feedback regulation of FSH secretion involves the actions of inhibin and testosterone and interactions between these hormones, but the physiologically relevant form of inhibin has not been determined. The mechanisms of action for inhibin are not known.

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Section: Regulation Of Fsh Secretion By Inhibinmentioning

confidence: 99%

Negative Feedback Regulation of the Secretion and Actions of Gonadotropin-Releasing Hormone in Males

Tilbrook

Clarke

2001

Biology of Reproduction

144

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“…The role of inhibin in regulating the production and secretion of FSH has been extensively documented in sheep, both in vivo (Martin et al 1988, Mann et al 1992, Tilbrook et al 1993 and in vitro (Clarke et al 1993, Muttukrishma & Knight 1994. The patterns of secretion of inhibin into the circulation, however, is less clear, due to limitations in the assays employed for its measurement.…”

Section: Introductionmentioning

confidence: 99%

Follicular waves and concentrations of steroids and inhibin A in ovarian venous blood during the luteal phase of the oestrous cycle in ewes with an ovarian autotransplant

Souza¹,

Campbell²,

Baird³

1998

Journal of Endocrinology

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The dynamics of ovarian follicular development and the pattern of pituitary and ovarian hormone concentration were investigated during the luteal phase in ewes with autotransplanted ovaries. The follicles were measured by ultrasound and samples of ovarian and jugular venous blood were collected at intervals of 12 h. Blood samples were collected before and after a GnRH challenge (250 ng GnRH, i.v.) to allow the determination of basal and LH-stimulated concentration of ovarian steroids. Throughout the luteal phase, large antral follicles developed in three waves, each of which was preceded by a rise in the concentration of FSH (P<0·05). The concentrations of oestradiol and androstenedione in the unstimulated and LH-stimulated samples were similar (P>0·05) during the first 3 days of the luteal phase but differed thereafter, with the LH-stimulated being significantly higher than the basal concentrations (P<0·05). In the first wave of follicular development the changes in follicular size were accompanied by an increase in the concentration of ovarian steroids and inhibin A. During the second follicular wave, although changes in follicle diameter were similar to the first wave (P>0·05), the basal concentration of ovarian steroids and inhibin A remained unchanged throughout the period of emergence and demise of the large follicles. These results confirm that the development of large antral follicles during the luteal phase of the sheep occurs in successive waves that are associated with fluctuations in FSH secretion. However, while the results strongly suggest that fluctuations in both inhibin A and oestradiol secretion control FSH during the first follicular wave, the cause of the FSH fluctuations associated with waves two and three is unclear. Final resolution of this issue may need to await the development of a specific assay for dimeric inhibin B.

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“…inhibin available in sufficient quantities, confirmed the inhibin-induced suppression of FSH secretion in adult rhesus monkeys (Ramaswamy et al, 1998) and rams (Tilbrook et al, 1993a) through a direct action at the pituitary (Tilbrook et al, 1993b). Furthermore, studies in castrated rams have indicated that inhibin acts synergistically with testosterone to maintain the normal feedback regulation of FSH secretion (Tilbrook and Clarke, 2001).…”

Section: Introductionmentioning

confidence: 72%

Production of inhibin A not B in rams: changes in plasma inhibin A during testis growth, and expression of inhibin/activin subunit mRNA and protein in adult testis

McNeilly

Souza²,

Baird³

et al. 2002

Reproduction

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Previous studies have shown that changes in the plasma concentrations of immunoreactive inhibin measured by radioimmunoassay occur in parallel with growth and regression of the testes during a reproductive cycle in adult Soay rams induced by exposure to an artificial lighting regimen of alternating 16 week periods of long days and short days. With the development of new two-site ELISAs for sheep inhibin A and inhibin B, we have re-examined the relationship between FSH and dimeric, biologically active inhibin in the reproductive cycle in adult Soay rams. No signal was generated by sheep testicular extract, ram or ewe plasma, or sheep ovarian follicular fluid in the inhibin B ELISA. In contrast, ram plasma contained significant activity in the inhibin A ELISA, which diluted in parallel to the inhibin A standard, and was abolished by preincubation of ram plasma with monoclonal antibodies specific for the betaA, but not the betaB, subunit. These results indicate that the ram is the first adult male mammalian species identified to date in which the testes produce and secrete dimeric inhibin A and not inhibin B. Northern blot analysis and immunocytochemistry confirmed the presence of alpha, betaA and betaB inhibin/activin subunit mRNA and protein in the testes of adult rams. Changes in plasma inhibin A concentrations occurred in parallel with the growth and regression of the testes during the long day: short day: long day lighting regimen in adult Soay rams, confirming our previous observations with immunoreactive inhibin. During the growth phase of the testes in the first 8 weeks of exposure to short days there was a positive correlation between plasma FSH and inhibin A concentrations, indicating that during this phase the secretion of inhibin A is stimulated by FSH and that inhibin A did not act as a negative feedback hormone on FSH secretion. From week 8.5 to week 16.0 of exposure to short days, there was a negative correlation between FSH and testosterone concentrations, but not inhibin, indicating that when inhibin concentrations are high, testosterone acts as the negative regulator of FSH secretion. Thus, in intact adult rams, when the testes are fully active it appears that inhibin A may sensitize the pituitary to the negative feedback effects of testosterone, at which time they act synergistically to maintain plasma concentrations of FSH.

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Human Recombinant Inhibin a Suppresses Plasma Follicle-Stimulating Hormone to Intact Levels but has No Effect on Luteinizing Hormone in Castrated Rams1

Cited by 40 publications

References 44 publications

Negative Feedback Regulation of the Secretion and Actions of Gonadotropin-Releasing Hormone in Males

Negative Feedback Regulation of the Secretion and Actions of Gonadotropin-Releasing Hormone in Males

Follicular waves and concentrations of steroids and inhibin A in ovarian venous blood during the luteal phase of the oestrous cycle in ewes with an ovarian autotransplant

Production of inhibin A not B in rams: changes in plasma inhibin A during testis growth, and expression of inhibin/activin subunit mRNA and protein in adult testis

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