Relative and combined effects of estradiol and prolactin on corticosterone secretion in ovariectomized rats

In vivo and in vitro experiments were designed to assess the relationship of the estradiol (E-2) and prolactin (PRL) on glucocorticoid secretion in ovariectomized (Ovx) rats. Female rats were Ovx for two weeks and then subcutaneously injected with oil or estradiol benzoate (EB) for 3 days before experimentation. Venous blood samples were collected from right jugular vein at 0, 30, 60, 90, and 120 min after challenge with adrenocorticotropin (ACTH). Adrenal zona fasciculata-reticularis (ZFR) cells from Ovx rats were isolated and incubated with E-2 or PRL. In the morning and afternoon, EB enhanced the basal and ACTH-stimulated concentrations of plasma corticosterone (CORT) and PRL. Administration of E, in vitro increased the basal and ACTH-stimulated release of CORT and production of adenosine 3', 5'-cyclic monophosphate (cAMP) in ZFR cells. E-2 enhanced the forskolin-stimulated release or CORT by ZFR cells. However, the 3-isobutyl-1-methylxanthine (IBMX)- or 8-Br-cAMP-stimulated release of CORT was not affected by E-2. E-2 augmented the lower doses of PRL-stimulated release of CORT and cAMP accumulation as compared with the PRL-treated group alone. Incubation of higher doses of PRL increased the production of cAMP. Administration of nifedipine and R(+) BK8644 (classic L-type Ca2+ channel blocker) significantly attenuated the PRL-stimulated release of CORT. Taken together, these data indicate that E-2- and PRL-related increase of CORT in Ovx rats is associated with the increase of cAMP accumulation and calcium influx in ZFR cells. In conclusion, E-2 and PRL play a stimulatory role in the co-regulation of CORT secretion.