Elevated luteinizing hormone induces expression of its receptor and promotes steroidogenesis in the adrenal cortex

Transgenic (TG) female mice expressing bLH beta-CTP (a chimeric protein der ived from the beta-subunit of bovine luteinizing hormone [LH] and a fragmen t of the beta-subunit of human chorionic gonadotropin [hCG]) exhibit elevat ed serum LH, infertility, polycystic ovaries, and ovarian tumors. In humans , increased LH secretion also occurs in infertility and polycystic ovarian syndrome, often concomitant with adrenocortical dysfunction. We therefore i nvestigated adrenal function in LH overexpressing bLH beta-CTP female mice. The size of their adrenals was increased by 80% with histological signs of cortical stimulation. Furthermore, adrenal steroid production was increase d, with up to 14-fold elevated serum corticosterone. Primary adrenal cells from TG and control females responded similarly to ACTH stimulation, but, s urprisingly, the TG adrenals responded to hCG with significantly increased cAMP, progesterone, and corticosterone production. LH receptor (LHR) expres sion and activity were also elevated in adrenals from female TG mice, but g onadectomized TG females showed no increase in corticosterone, suggesting t hat the dysfunctional ovaries of the intact TG females promote adrenocortic al hyperfunction. We suggest that, in intact TG females, enhanced ovarian e strogen synthesis causes increased secretion of prolactin (PRL), which elev ates LHR expression. Chronically elevated serum LH, augmented by enhanced P RL production, induces functional LHR expression in mouse adrenal cortex, l eading to elevated, LH-dependent, corticosterone production. Thus, besides polycystic ovaries, the bLH beta-CTP mice provide a useful model for studyi ng human disorders related to elevated LH secretion and adrenocortical hppe rfunction.