Estradiol and Plasminogen Activator Secretion by Cultured Rat Sertoli Cells in Response to Melanocyte‐Stimulating Hormones

Abstract

Pro‐opiomelanocortin‐derived peptides, α‐MSH and β‐endorphin, are synthesized and secreted by Leydig cells, and are believed to have paracrine effects on Sertoli cells in the testis. Peptides with MSH activity stimulate adenylate cyclase and cAMP accumulation in Sertoli cell‐enriched cultures. The purpose of the present study was to determine whether such peptides would affect Sertoli cell parameters, such as aromatase and plasminogen activator activities, that are known to be regulated by cAMP, α‐MSH stimulated aromatase activity in Sertoli cell‐enriched cultures prepared from 10‐day‐old rats and this effect was potentiated by methyl isobutylxanthine (MIX). The combination of α‐MSH plus MIX was not as potent as FSH. α‐MSH, des‐acetyl‐α‐MSH, β‐MSH, ACTH(1–13), and ACTH(1–24) stimulated aromatase activity to a similar extent, suggesting that Sertoli cells do not distinguish between the activities of these peptides. α‐MSH potentiated the action of dbcAMP and forskolin on Sertoli cell aromatase, but unexpectedly had no effect on the action of either half‐maximal or maximal doses of FSH. The regulation of plasminogen activator was examined next; urokinase was markedly suppressed by FSH in 10‐day‐old Sertoli cells. Although neither α‐MSH nor MIX alone had an effect on urokinase secretion, in combination they were as effective as FSH. In 10‐day‐old Sertoli cells each of these peptides had little or no effect on tissue plasminogen activator. It was concluded that molecules such as the MSH/ACTH peptides modulate Sertoli cell function via cAMP, that there is a differential response depending more upon the Sertoli cell products examined rather than the peptide tested, and that the magnitude of the responses to α‐MSH and MIX examined to date do not exceed those produced by FSH. 1989 American Society of Andrology