title: Elevated luteinizing hormone induces expression of its receptor and promotes steroidogenesis in the adrenal cortex.
abstract: Transgenic (TG) female mice expressing bLHbeta-CTP (a chimeric protein derived from the beta-subunit of bovine luteinizing hormone [LH] and a fragment of the beta-subunit of human chorionic gonadotropin [hCG]) exhibit elevated 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 investigated adrenal function in LH overexpressing bLHbeta-CTP female mice. The size of their adrenals was increased by 80% with histological signs of cortical stimulation. Furthermore, adrenal steroid production was increased, with up to 14-fold elevated serum corticosterone. Primary adrenal cells from TG and control females responded similarly to ACTH stimulation, but, surprisingly, the TG adrenals responded to hCG with significantly increased cAMP, progesterone, and corticosterone production. LH receptor (LHR) expression and activity were also elevated in adrenals from female TG mice, but gonadectomized TG females showed no increase in corticosterone, suggesting that the dysfunctional ovaries of the intact TG females promote adrenocortical hyperfunction. We suggest that, in intact TG females, enhanced ovarian estrogen synthesis causes increased secretion of prolactin (PRL), which elevates LHR expression. Chronically elevated serum LH, augmented by enhanced PRL production, induces functional LHR expression in mouse adrenal cortex, leading to elevated, LH-dependent, corticosterone production. Thus, besides polycystic ovaries, the bLHbeta-CTP mice provide a useful model for studying human disorders related to elevated LH secretion and adrenocortical hyperfunction.
authors.affiliation: Department of Physiology, and. Department of Pediatrics, University of Turku, FIN-20520 Turku, Finland. Department of Pathology, Glasgow Royal Infirmary, Castle Street, Glasgow G4 0SF, United Kingdom.
authors.forename: J
authors.initials: J
authors.lastname: Kero
authors.forename: M
authors.initials: M
authors.lastname: Poutanen
authors.forename: F P
authors.initials: FP
authors.lastname: Zhang
authors.forename: N
authors.initials: N
authors.lastname: Rahman
authors.forename: A M
authors.initials: AM
authors.lastname: McNicol
authors.forename: J H
authors.initials: JH
authors.lastname: Nilson
authors.forename: R A
authors.initials: RA
authors.lastname: Keri
authors.forename: I T
authors.initials: IT
authors.lastname: Huhtaniemi
mesh_terms: D000302:Adrenal Cortex / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000367:Age Factors; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000235:genetics / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood; D005260:Female; D006651:Histocytochemistry; D017403:In Situ Hybridization; D007986:Luteinizing Hormone / Q000097:blood* / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011374:Progesterone / Q000378:metabolism; D011388:Prolactin / Q000097:blood; D012333:RNA, Messenger / Q000378:metabolism; D011974:Receptors, LH / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D013256:Steroids / Q000096:biosynthesis*
chemical_list: D006063:Chorionic Gonadotropin; D012333:RNA, Messenger; D011974:Receptors, LH; D011993:Recombinant Fusion Proteins; D013256:Steroids; D011374:Progesterone; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D007986:Luteinizing Hormone; D003345:Corticosterone