Age-related variation of follicle-stimulating hormone-stimulated cAMP production, protein kinase C activity and their interactions in the rat testis

Abstract

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 α, β and γ in rat testes between day 19 of fetal life and day 90 postpartum. Human FSH (30 mg/1) 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 α isoenzyme (maximum on day 10), whereas those of PKC γ and PKC β 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 α. At the same tune, 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.