ENDORPHIN SUPPRESSES FSH-STIMULATED PROLIFERATION OF ISOLATED NEONATAL SERTOLI CELLS BY A PERTUSSIS TOXIN-SENSITIVE MECHANISM

During perinatal development, when the size of the Sertoli cell population is determined, Leydig cells produce β‐endorphin, a peptide which may interact with Sertoli cells to modify their FSH‐responsiveness, as suggested by our previous work. The goal of the present study was first, to test directly the possibility that β‐endorphin modifies the proliferative response of neonatal Sertoli cells to FSH, and second, to gain information on a mechanism(s) involved in any observed effect. We treated isolated 6‐day‐old Sertoli cells with FSH or vehicle in vitro and measured their incorporation of exogenous, radiolabeled thymidine with quantitative autoradiography. After 2 days in culture with FSH, we detected a 10‐fold increase in the rate of Sertoli cell proliferation. The level of cell division in these FSH‐treated cultures was identical to that in other cultures exposed to cAMP under similar conditions. In addition, inclusion of β‐endorphin 3 hr prior to FSH or cAMP decreased the effect of the hormone by 50% but left the cAMP response unchanged. Thus, β‐endorphin acts on isolated, neonatal Sertoli cells at a point prior to intracellular production of cAMP to suppress their response to FSH. When other cultures were treated with pertussis toxin, a blocker of intracellular GTP‐binding proteins such as Gi, before sequential addition of endorphin and FSH, the effect of β‐endorphin on FSH‐responsiveness was abolished. Moreover, when other cultures were exposed to pertussis toxin in the absence of endorphin, followed by FSH, their response to the hormone was unchanged. Thus, β‐endorphin apparently modifies the proliferative response of neonatal Sertoli cells to FSH via a mechanism involving one or more G proteins. These observations, along with our previous data showing enhanced Sertoli cell division in vivo in the presence of an opiate blocker, point to the existence of endorphin‐mediated communication between Leydig and Sertoli cells during perinatal development and provide new evidence suggesting that paracrine mechanisms modify Sertoli cell function during perinatal development, when the size of this population is established. Copyright © 1990 Wiley‐Liss, Inc.