AGE-RELATED VARIATION OF FOLLICLE-STIMULATING HORMONE-STIMULATED CAMP PRODUCTION, PROTEIN-KINASE-C ACTIVITY AND THEIR INTERACTIONS IN THE RAT TESTIS

To study further the ontogeny of hormonal regulatory mechanisms in the testis, we measured follicle-stimulating hormone (FSH)- and protein kinase C (PKC)-stimulated cAMP production, PKC activity, and messenger (m)RNA levels of the PKC isoenzymes alpha, beta and gamma in rat testes between day 19 of fetal life and day 90 postpartum. Human FSH (30 mg/l) stimulated slightly but significantly cAMP production of fetal testes (57%; p < 0.05). A higher response (3-fold; p < 0.01) was observed on the day of birth, and the maximum FSH effect on cAMP (23-fold) was observed on day 10 postpartum. Thereafter, a gradual decline of FSH response occurred towards adult age. Concerning testicular PKC, the soluble (inactive) form had its maximum at the age of 1 day and this PKC form declined gradually thereafter. The particulate (active) form was low at birth, increased 6-fold on days 8-11 of age, and declined thereafter. A significant age-dependent variation was also found in the mRNA level of the PKC alpha isoenzyme (maximum on day 10), whereas those of PKC gamma and PKC beta were undetectable at all ages in Northern blots. When the in vitro modulation of basal and FSH-dependent cAMP production by the PKC activator 12-O-tetradecanoylphorbol 13-acetate (TPA, 100 nmol/1) was studied, the substance alone was without effect at all ages studied. The TPA effect on FSH-stimulated cAMP production displayed age-dependent variation: a slight stimulation in fetal testes, no effect at birth, decrease between days 8 and 11, and no effect on day 30. In conclusion, the FSH-stimulated cAMP production is at its maximum in rat testicular tissue on days 8-11 postpartum. The age of maximum cAMP production is associated with a sharp peak in the active form of PKC and in the mRNA level of PKC isoenzyme alpha. At the same time, a transition appears to occur from stimulation to inhibition in the modulatory effect of PKC on FSH-stimulated cAMP production. Thus, clearcut developmental changes occur in testicular FSH action and its modulation by the PKC-related signal transduction systems.