Abstract
Estrogen plays a critical role in inducing LH surge. In the pituitary, estrogen receptor α (ERα) mediates the action of estrogen, while the downstream pathway of ERα activation is yet to be elucidated. Here, we report the finding that cholecystokinin type A receptor (CCK-AR) is an ERα 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 ERα gene completely abolish CCK-AR mRNA expression. Injection of 17β-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 ERα 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 ERα downstream gene in the pituitary and suggests that CCK-AR may play a role in the estrogen sensitization of the pituitary response to GnRH.
Original language | English (US) |
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Pages (from-to) | 393-405 |
Number of pages | 13 |
Journal | Journal of Endocrinology |
Volume | 195 |
Issue number | 3 |
DOIs | |
State | Published - Dec 2007 |
Externally published | Yes |
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Endocrinology