A NEW TARGET FOR GROWTH-HORMONE RELEASING-HORMONE ACTION IN RAT - THESERTOLI-CELL

A GHRH-like mRNA and peptide (t-GHRH) have been detected in rat and hu man testis. In rat, t-GHRH mRNA is localized to developing spermatogen ic cells. We predicted that the most likely target cell of t-GHRH acti on would be the Sertoli cell. To test this prediction, we evaluated GH RH action on Sertoli cell function. Rat GHRH at a concentration of 10 nM or 100 nM stimulated cAMP production 2-fold over control levels aft er a 30 min incubation. This stimulation was obliterated by preincubat ion with a 10- fold excess of the GHRH antagonist (N-Ac-Tyr1, D-Arg2)- GRF(1-29)-NH2. The effect of treatment with [His1, Nle27]GHRH(I-32)-NH 2, a GHRH analog, on Sertoli cell mRNAs was also assessed. Treatment w ith the analog significantly increased levels of c-fos and steel facto r (the product of the Steel gene, also termed SCF) mRNAs above control s, but had no effect on sulfated glycoprotein-2 mRNA. We conclude that GHRH acts via adenylate cyclase to modulate specific Sertoli cell pro ducts, possibly as part of a network of local interacting factors cont rolling Sertoli and germ cell function.