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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<0·001) and GnRH-induced (+25%; P<0·001) release of FSH as well as in the residual cell content (+114%; P<0·001) and total FSH content/well (+67%; P<0·001). Conversely, inhibin significantly (P<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<0·001) of GnRH-induced LH release. This was associated with a corresponding increase (P<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<0·001) GnRH-induced LH release. This was associated with a corresponding fall (P<0·001) in residual cellular content of LH. Neither activin-A nor inhibin significantly affected total LH content/well, indicating a lack of effect of either agent on LH biosynthesis.
Comparison of the dose-dependent effects of inhibin on FSH and LH production by cells cultured in the presence and absence of a fixed dose level of activin-A (5 ng/ml) revealed a significant (P<0·01) interaction between the two agents which appeared to be of a non-competitive nature.
These findings support the concept that both activin and inhibin participate in the gonadal feedback control of pituitary FSH secretion in the sheep. They also indicate that both agents are capable of modulating GnRH-induced LH secretion in this species.
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