PASSIVE IMMUNONEUTRALIZATION WITH A MONOCLONAL-ANTIBODY REVEALS A ROLE FOR ENDOGENOUS ACTIVIN-B IN MEDIATING FSH HYPERSECRETION DURING ESTRUS AND FOLLOWING OVARIECTOMY OF HYPOPHYSECTOMIZED, PITUITARY-GRAFTED RATS

Recently, we reported that ovariectomy (OVX)-induced FSH hypersecretion can be elicited in hypophysectomized rats bearing renal pituitary allografts isolated from direct hypothalamic intervention. The possible role of the FSH-stimulating protein, activin-B, in eliciting this response was investigated using passive immunoneutralization with a monoclonal antibody (MAb) generated against activin-B. Other hypophysectomized/pituitary-grafted (H/G) rats serving as controls received an equivalent amount of a MAb incapable of neutralizing the biological actions of activin-B. Administration of increasing doses of the MAb prior to OVX dose-dependently suppressed serum FSH levels 12 h after OVX. Less consistent effects were observed 24 h after OVX even though an additional injection of the MAb was given 12 h after OVX in one study. SInce it has been postulated that the periovulatory increase in FSH secretion on estrus which is important for recruitment of follicles is a hypothalamic-independent phenomena, a separate experiment was performed in order to ascertain whether a local regulatory mechanism involving activin-B is operative on estrus. As in the preceding study using H/G rats, administration of the activin-B MAb on the evening of proestrus significantly attenuated serum FSH rises early on estrus. These results are consonant with the evolving concept that an important mechanism exists within the anterior pituitary proper for regulation of FSH secretion that involves the autocrine actions of activin-B.