Catherine Laure Rivier

Modulation of Gonadotropin Secretion by Proteins of the Inhibin Family: Studies in the Female Rat

The secretion of FSH by anterior pituitary gonadotropes is controlled by both brain factors and those of peripheral origin. Gonadotropin releasing hormone (GnRH), a decapeptide originally characterized in mammalian hypothalamus (1, 2), stimulates FSH secretion in a variety of animal models; removal of GnRH, or blockade of its receptors, decreases basal FSH levels (reviewed in 3). However, several observations have suggested that existence of factors other than GnRH as major regulators of FSH secretion: Administration of GnRH antisera or antagonists to rats does not completely obliterate FSH release (4–10); LH can trigger a rise in FSH levels despite blockade of GnRH receptors (6) (a phenomenon that, as described below, is probably mediated through inhibin); and destruction of the dorsal anterior hypothalamus reduces LH, but not FSH, secretion by ovariectomized rats (11). At present, this GnRH-independent component of FSH release is believed to include sex steroids and gonadal proteins, such as inhibin, activin, and follistatin (reviewed in 12–114). The recent availability of recombinant human (rh) inhibin A has allowed us to reexamine the effect of this protein in a variety of animal models. Additionally, rh inhibin, combined with GnRH antagonists and inhibin antibodies, is proving to be a powerful tool with which to investigate the respective physiological role and pharmacological effects of GnRH and gonadal proteins in modulating reproductive functions.

Role of Endogenous Corticotropin-Releasing Factor in Modulating the Pituitary Response to Stress

The exposure of rats to stressful stimuli results in increased adrenocorticotropic hormone (ACTH) secretion with decreased luteinizing hormone (LH) and growth hormone (GH) release. Since corticotropin-releasing factor (CRF) is also released during stress1, we investigated the possibility that changes in its endogenous levels might mediate the effect of stress on pituitary function.