Regulation of Adrenal and Testicular Prolactin Receptors by Adrenocorticotropin and Luteinizing Hormone

Receptors for PRL in the adrenal, ovary, and testis undergo marked and rapid depletion after trophic stimulation by ACTH and LH, respectively. The mechanism of such heterologous regulation of PRL receptors in the testis and adrenal cortex was further analyzed in hormone-treated male rats. Hormone-stimulated turnover of PRL receptors was not prevented by treatment with cycloheximide (75 and 300 μg), which caused an 80% fall in testicular and adrenal sites within 1 h, followed by a return to normal in 24 h. When steroid secretion was inhibited by treatment with 4-aminopyrazolopyrimidine for 4 days, with a 90% decrease in serum cholesterol, ACTH and LH retained the ability to reduce PRL receptors by 60–70% 12 and 24 h after injection. Similarly, during blockade of steroidogenesis by aminoglutethimide, treatment with 10 U ACTH or 100 μg ovine LH still reduced PRL receptors by about 70%. When adrenal and testicular steroidogeneses were stimulated by the administration of 8-bromo cAMP, serum corticosterone and testosterone were increased by 10-fold after 1 h, but there was no decrease in PRL receptors at the later times (12 and 24 h) when ACTH and LH caused marked receptor depletion. However, an early increase of 20–40% in PRL receptors was observed 1 h after treatment with 8-bromo cAMP, corresponding to the phase of increased steroid secretion. Similar increases in PRL receptors were evident in the adrenal and testis 1 h after treatment with the respective trophic hormones, again when steroid secretion was elevated. These early changes in adrenal and testicular PRL receptors after hormonal stimulation were completely inhibited in aminoglutethimide-treated rats, indicating their dependence on steroid secretion. These findings demonstrate that PRL receptors undergo rapid depletion in rat adrenal cortex and testis after trophic hormone stimulation. The mechanism by which ACTH and LH cause depletion of PRL receptors does not appear to depend upon cAMP-mediated responses, and may represent a form of concomitant receptor processing at the cell membrane level. The early increase in adrenal and testicular PRL receptors caused by trophic hormones and 8-bromo cAMP occurs during the phase of increased steroid secretion, and probably reflects changes in membrane conformation that accompany the steroid secretory response.