Steroidal and peptidic control mechanisms in membrane of Xenopus laevis oocytes resuming meiotic division.

Stage 5-6 Xenopus laevis oocytes are arrested in the prophase of the first meiotic division, and can be studied in vitro after removal from their follicle cell environment. While they do not mature spontaneously, they demonstrate germinal vesicle (nucleus) breakdown (GVBD) if exposed to approximately 1 microM progesterone, the hormone released in vivo at the time of ovulation and maturation. They become an egg ready to be fertilized. The progesterone-oocyte interaction, contrary to what is observed in endocrine steroid target organs so far studied, takes place at the surface membrane level and is not narrowly progesterone specific, since other hormones such as cortisol or testosterone also can resume meiosis in vitro. This is the first description of such a paracrine steroid system, which depends however on a receptor mechanism, as revealed by physico-chemical experiments, studies with antagonistic (competitive) steroids, and cell-free specific inhibitory effects on membrane bound adenylate cyclase. It was found that insulin and related growth factors (MSA, IGF) are also meiosis reinitiators. Insulin potentiates low progesterone concentration (approximately 1 nM), also in completely denuded oocytes (free of the vitelline membrane). From these observations, it is suggested that there may be a physiological cooperative involvement of a steroid (progesterone) and an insulin-like peptidic factor within the ovaries to promote oocyte maturation in vivo. The molecular mechanisms implicated in the hormone-dependent changes of c-AMP and Ca2+ remain to be elucidated in detail, as well as the respective role of these two sets of metabolic events.