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Effect of Recombinant Activin-A on Gonadotropin Secretion in the Female Rat^*

CATHERINE RIVIER and WYLIE VALE

The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute La Jolla, California 92037

Address all correspondence and requests for reprints to: Dr. Catherine Rivier, The Salk Institute, P.O. Box 85800, San Diego, California 92186-5800.

Abstract

Repeated injections of recombinant human (rh) activin-A over a 2- to 3-day period are reportedly needed to stimulate the in vivo secretion of FSH. In this paper we present results showing that acute treatment with rh-activin-A caused marked and dose-dependent increases in plasma FSH, but not LH, levels in adult female rats. After one injection, maximum FSH release was observed 4 h after the administration of activin, while two injections of 100 ng activin/kg, 5 h apart, maintained elevated FSH levels for more than 10 h in intact diestrous day 1 females. Removal of the GnRH drive by pretreatment of ovariectomized animals with the GnRH antagonist ([Ac- D2Nal1,DCpa2,D3Pal3,Arg8,D-p-methoxyphenyl)5-oxo-2-aminopentanoic acid6,DAlaI0]GnRH; 100 /tg/kg;) or repeated injections of the GnRH agonist ([DTrp6,Pro9,NEt,NH2]GnRH; 1 Mg/h for 5 days) did not prevent the stimulatory action of activin. Concomitant treatment with rh-inhibin-A (30 jig/kg)), on the other hand, completely blocked FSH secretion induced by 100 ng activin/kg.

These results indicate that activin-A is a powerful stimulus for FSH secretion in the female rat and exerts this effect independently of GnRH. (Endocrinology 129: 2463–2465,1991)

Footnotes

^* This work was supported by NIH Grant HD-13527 and was conducted in part by the Clayton Foundation for Research, California Division.

Clayton Foundation investigator.

Received April 21, 1991.

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