Abstract
BackgroundActivin and inhibin are glycoproteins structurally related to the transforming growth factor-beta superfamily. These peptides were first described as factors that regulate the follicle-stimulating hormone (FSH) at the pituitary level. The possible role of inhibin and activin, at the ovarian level, in mediating the stimulatory actions of a Fundulus pituitary extract (FPE) and 17alpha,20beta-dihydroprogesterone (DHP) on oocyte maturation was investigated in this study.MethodsIn vitro culture of ovarian follicles and induction of oocyte maturation were carried out in 75% Leibovitz L-15 medium. Follicles or denuded oocytes were exposed to FPE, inhibin, activin, ethanol vehicle (control group), or DHP. The competence of the follicles or denuded oocytes to respond to the hormones was assessed by scoring germinal vesicle breakdown (GVBD) used as an indication of the reinitiation of meiosis or oocyte maturation. DHP level was measured by radioimmunoassay.ResultsAddition of FPE promoted the synthesis of DHP by the granulose cells of fully grown ovarian follicles and thus stimulated GVBD in the oocyte. Presence of porcine inhibin did not hinder the synthesis of DHP stimulated by FPE, although it did inhibit the subsequent GVBD in a dose-dependent manner, suggesting that the action of inhibin was at the oocyte level. Similarly to the findings with FPE, inhibin also blocked the DHP-induced GVBD in intact follicles, as well as the spontaneous and steroid-induced GVBD of denuded oocyte. Inhibin straightforwardly blocked the response to a low dose of DHP throughout the culture period, while higher doses of the steroid appeared to overcome the inhibitory effect especially at later times. In contrast to inhibin, recombinant human activin A significantly enhanced DHP-induced GVBD in a dose-dependent manner after 48 hr, although activin alone was not able to induce GVBD without the presence of the steroid.ConclusionTaking together with our previous studies that demonstrate the presence of activin/inhibin subunits in the ovary of F. heteroclitus, these in vitro findings indicate that inhibin and activin are local regulators in the teleost ovary and have opposing effects in modulating oocyte maturation.
Highlights
Activin and inhibin are glycoproteins structurally related to the transforming growth factor-beta superfamily
Inhibin effects on oocyte maturation induced by gonadotropin It has been well documented that addition of Fundulus pituitary extract (FPE) to F. heteroclitus intact follicles cultured in vitro promotes an increase in the synthesis of 17α,20β-dihydroprogesterone (DHP) by the granulosa cells [33,38]
The maximum response to FPE in terms of germinal vesicle breakdown (GVBD) occurred at 72 hr, and a consistent dosedependent inhibitory effect of inhibin was observed throughout the entire incubation period (Fig. 1A)
Summary
Activin and inhibin are glycoproteins structurally related to the transforming growth factor-beta superfamily These peptides were first described as factors that regulate the folliclestimulating hormone (FSH) at the pituitary level. Activins are composed of two β subunits in any combination [1] These peptides, found in mammalian follicular fluids, were first described as factors that regulate the follicle-stimulating hormone (FSH) at the pituitary level [2,3,4]. Activin and inhibin have been implicated in oocyte maturation, albeit conflicting evidence has been reported In this regard, inhibin was shown to have no effect [8] or to inhibit spontaneous division in both cumulus enclosed and denuded oocytes from immature rats [9] and to suppress luteinizing hormone-induced meiosis in follicle-enclosed oocytes of preovulatory rats [8]. It is well known that in lower vertebrates, oocyte maturation is triggered by a surge of gonadotropin hormones that, acting in the granulose cells, increases the production of progestogens, which action on the oocyte initiates germinal vesicle breakdown (GVBD), or oocyte maturation
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