Protein kinase inhibitor in sertoli cell-enriched rat testis. Specific regulation by follicle-stimulating hormone.

The CAMP-dependent protein kinase (EC 2.7.1.37; ATP:protein phosphotransferase) inhibitor in Sertoli cell-enriched rat testis has been shown to be specifically stimulated by follicle-stimulating hormone in uiuo. Intraperitoneal injection of follicle-stimulating hormone (100 pg of NIH-FSH-S12) induced a significant increase in protein kinase inhibitor 8 h after injection. Maximal stimulation of inhibitor activity (a-fold) was achieved with 24 h of hormone treatment (two injections at 12-h intervals). Stimulation of inhibitor activity by follicle-stimulating hormone was dependent upon the age of the animal; inhibitor activity was increased by hormone treatment in 12and 19-day-old rats but not in animals 32 days of age. However, hypophysectomy of 30-day-old rats restored the ability of inhibitor to respond to hormone treatment. Hypophysectomy caused a rapid and sharp drop (4to &fold) in inhibitor activity but subsequent administration of follicle-stimulating hormone 6 and 13 days later revealed significant 2and 4-fold increases in inhibitor activity, respectively. Under conditions where protein kinase inhibitor was stimulated, the specific activity of CAMPdependent protein kinase was reduced significantly. Stimulation of inhibitor activity was specific to follicle-stimulating hormone; neither luteinizing hormone nor testosterone proprionate could induce any increase in protein kinase inhibitor activity. Near maximal enhancement of inhibitor activity was achieved with 5 gg of purified follicle-stimulating hormone (Papkoff) administered intraperitoneally. Hormonal stimulation of protein kinase inhibitor was dependent upon continued protein synthesis; cycloheximide completely prevented hormone-dependent increases in inhibitor content. Protein kinase inhibitor and CAMP-dependent protein kinase activities were also compared during postnatal development. In particular, a sharp spike of inhibitor specific activity occurs at 19 days of age, a time when the Sertoli cell is rapidly losing its sensitivity to follicle-stimulating hormone. At this time, inhibitor could inactivate as much as 41% of the total testicular pool of catalytic subunit of CAMP-dependent protein kinase.