title: Estrogen receptor alpha-induced cholecystokinin type A receptor expression in the female mouse pituitary.
abstract: Estrogen plays a critical role in inducing LH surge. In the pituitary, estrogen receptor alpha (ERalpha) mediates the action of estrogen, while the downstream pathway of ERalpha activation is yet to be elucidated. Here, we report the finding that cholecystokinin type A receptor (CCK-AR) is an ERalpha downstream gene in the mouse anterior pituitary. In the cycling mouse pituitary, the expression of CCK-AR mRNA is markedly higher in the afternoon of proestrus compared with metestrus. Both ovariectomy (OVX) and null mutation of the ERalpha gene completely abolish CCK-AR mRNA expression. Injection of 17beta-estradiol to OVX wild-type mice induces recovery of CCK-AR mRNA expression to levels observed at proestrus, but no such recovery is induced in OVX ERalpha knockout mice. The same pattern of estrogen dependency in inducing CCK-AR mRNA expression was seen in cultured primary anterior pituitary cells, indicating that estrogen directly acts on pituitary cells to induce CCK-AR expression. Immunohistological analysis revealed that more than 80% of gonadotrophs express CCK-AR in the afternoon of proestrus. To test whether CCK-AR mediated the sensitizing effect of estrogen in GnRH-induced LH secretion, primary pituitary cells were primed with estrogen followed by treatment with GnRH in the presence or absence of lorglumide, a CCK-AR antagonist. While both groups secreted LH upon GnRH treatment, lorglumide treatment significantly decreased LH secretion. Taken together, this study finds CCK-AR to be an ERalpha downstream gene in the pituitary and suggests that CCK-AR may play a role in the estrogen sensitization of the pituitary response to GnRH.
authors.affiliation: Division of Clinical and Reproductive Sciences, Department of Clinical Sciences, University of Kentucky, Lexington, Kentucky 40536, USA.
authors.forename: Hyun Joon
authors.initials: HJ
authors.lastname: Kim
authors.forename: Mary C
authors.initials: MC
authors.lastname: Gieske
authors.forename: Susan
authors.initials: S
authors.lastname: Hudgins
authors.forename: Beob Gyun
authors.initials: BG
authors.lastname: Kim
authors.forename: Andree
authors.initials: A
authors.lastname: Krust
authors.forename: Pierre
authors.initials: P
authors.lastname: Chambon
authors.forename: Chemyong
authors.initials: C
authors.lastname: Ko
mesh_terms: D000818:Animals; D002452:Cell Count; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000172:deficiency / Q000502:physiology*; D005260:Female; D052681:Gonadotrophs / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010052:Ovariectomy; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011359:Proestrus / Q000502:physiology; D011377:Proglumide / Q000031:analogs & derivatives / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D043886:Receptor, Cholecystokinin A / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D047628:Estrogen Receptor alpha; D012333:RNA, Messenger; D043886:Receptor, Cholecystokinin A; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D007986:Luteinizing Hormone; D011377:Proglumide; C048181:lorglumide