Corticotropin-releasing factor can stimulate gonadotropin secretion by human fetal pituitaries in superfusion

Abstract

In previous studies, corticotropin-releasing factor was found to elicit a rise in circulating adrenocorticotropic hormone in human subjects and laboratory animals, but no stimulatory effect of corticotropin-releasing factor on other pituitary hormones was detected. Since stress may be associated with luteinizing hormone changes as well as with those of corticotropin-releasing factor and adrenocorticotropic hormone, we quantified gonadotropin responses to corticotropin-releasing factor and arginine vasopressin in 11 human fetal pituitaries with use of both superfusions and static incubations. Exposure to corticotropin-releasing factor brought about a significant increase in adrenocorticotropic hormone and gonadotropin concentrations in the effluent media by means of the superfusion system. Similar concentrations of corticotropin-releasing factor significantly increased adrenocorticotropic hormone secretion into the medium by dispersed fetal pituitary cells cultured on an extracellular matrix but failed to increase luteinizing hormone and follicle-stimulating hormone secretion. Exposure to 3 mmol/L 8-bromo-cyclic adenosine monophosphate caused an increase in all three peptides, both in superfusion and static incubations. Dose-response studies showed that the effect on gonadotropin secretion occurred at concentrations of 8-bromocyclic adenosine monophosphate two orders of magnitude lower than those affecting adrenocorticotropic hormone secretion. The purity of corticotropin-releasing factor and arginine vasopressin used in these studies was confirmed by high-performance liquid chromatography. These in vitro results are consistent with a paracrine effect of corticotropes acting on gonadotropes. The combination of static incubation and superfusion has proved useful in elucidating the effects of different secretagogues on pituitary cells.