h-89 and Hyperprolactinemia

To evaluate the effects of hyperprolactinemia on aldosterone secretion and its mechanisms of action in ovariectomized (OVX) rats.. Hyperprolactinemia was induced by the transplantation of rat anterior pituitary (AP) glands under the kidney capsule for 6 weeks in female rats. Control rats underwent cerebral cortex (CX) transplantation. Four weeks after transplantation, the rats were OVX 2 weeks before decapitation. After decapitation, the trunk blood was collected, and the adrenal glands of CX- and AP-grafted rats were prepared as zona glomerulosa (ZG) cells for in vitro study.. Plasma prolactin and aldosterone in the rats were increased by AP gland transplantation. In the in vitro study, the basal aldosterone secretion by the adrenal ZG cells was higher in AP-grafted rats than in CX-grafted rats. The AP-grafted group showed increased responsiveness to angiotensin II (10(-8) M), KCl (8 x 10(-3) M), or 8-bromo-adenosine 3',5'-cyclic monophosphate (8-br-cAMP; 10(-4) M, a membrane-permeable analogue of cAMP) with regard to aldosterone secretion as compared with the CX-grafted group. N-(2-[p-Bromocinnamylamine]ethyl)-5-isoquinolinesulfonamide (H89; 10(-6), 10(-5) M, a protein kinase A inhibitor) or tetrandrine (10(-5) M, a blocker for both L-type and T-type Ca2+ channels) induced a greater suppression of aldosterone secretion in the AP-grafted group than in the CX-grafted group. No significant differences between the CX- and AP-grafted groups were observed, however, with regard to the adrenocorticotropichormone (10(-9) M)-, forskolin (10(-5) M, an adenylyl cyclase activator)-, or nifedipine (10(-5) M, an L-type Ca2+ channel blocker)-induced responsiveness of aldosterone secretion. In addition, there was no difference in the expression of desmolase (i.e., cytochrome P450 side-chain cleavage enzyme) in ZG cells between AP- and CX-grafted rats. The conversions of 25-OH-cholesterol into pregnenolone in the presence of trilostane (an inhibitor of 3beta-hydroxysteroid dehydrogenase) and corticosterone into aldosterone, as well as the expression of the steroidogenic acute regulatory protein in ZG cells, were greater in AP-grafted rats than in CX-grafted rats.. These results suggest that hyperprolactinemia increases basal, angiotensin II- and KCl-stimulated aldosterone secretion by ZG cells in OVX rats through activation of T-type Ca2+ channels, the post-cAMP and protein kinase A pathway, cytochrome P450 side-chain cleavage enzyme, and aldosterone synthase, as well as by causing increased expression of steroidogenic acute regulatory protein in ZG cells.

Topics: 8-Bromo Cyclic Adenosine Monophosphate; Adenylyl Cyclases; Aldosterone; Alkaloids; Angiotensin II; Animals; Benzylisoquinolines; Calcium Channels, T-Type; Cells, Cultured; Cholesterol Side-Chain Cleavage Enzyme; Cyclic AMP-Dependent Protein Kinases; Cytochrome P-450 CYP11B2; Female; Hyperprolactinemia; Isoquinolines; Ovariectomy; Phosphoproteins; Pituitary Gland, Anterior; Potassium Chloride; Prolactin; Rats; Rats, Sprague-Dawley; Sulfonamides; Zona Glomerulosa