Steroid and peptide control mechanisms in membrane of Xenopus laevis oocytes resuming meiotic division.

Stage 5-6 Xenopus laevis oocytes are arrested in 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). The oocytes' then become eggs ready to be fertilized. The progesterone-oocyte interaction, contrary to what is observed in all 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 can also cause resumption of meiosis in vitro. This is the first description of such a paracrine steroid system, which depends however on a receptor mechanism, as indicated by physicochemical 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 (mitosis-stimulating activity, MSA; insulin-like growth factor, IGF) are also reinitiators of meiosis. Insulin also potentiates the effects of low progesterone concentration (approximately 1 nM) 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 peptide factor within the ovaries which promotes oocyte maturation in vivo. The molecular mechanisms of the hormone-dependent changes in cyclic AMP and Ca2+ remain to be elucidated in detail, as well as the respective roles of these two sets of metabolic events.