Sexually dimorphic expression of corticotropin-releasing hormone-binding protein in the mouse pituitary.
In the pituitary, CRH-binding protein (CRH-BP) neutralizes the ACTH-releasing activity of CRH. Because sexual dimorphisms exist at multiple levels of the hypothalamic-pituitary-adrenal axis, these studies examined expression of pituitary CRH-BP in the male and female mouse pituitary. Ribonuclease protection assays and (125)I-CRH cross-linking assays demonstrate greater expression of pituitary CRH-BP in female than male mice. Normalized CRH-BP mRNA levels in female mice are 2.58 times greater at proestrus than diestrus. Ovariectomy reduces pituitary CRH-BP mRNA levels to 11% of sham-ovariectomy control levels, and estradiol benzoate treatment restores CRH-BP mRNA to control levels. These data suggest that estrogen positively regulates pituitary CRH-BP. Dual in situ hybridization analysis reveals that CRH-BP expression increases significantly in proopiomelanocortin-expressing cells at proestrus, compared with metestrus (P = 0.003), suggesting that CRH-BP expression is estrogen regulated in corticotropes. Further studies reveal that approximately 80% of the CRH-BP transcripts in the proestrus mouse pituitary localize to prolactin-expressing cells, a novel site for CRH-BP expression. CRH-BP mRNA levels increase significantly at proestrus, compared with metestrus in prolactin-positive cells (P < 0.0001). This robust, estrogen-regulated expression of CRH-BP in lactotropes in female mice suggests that the pituitary is an important site for interactions between the hypothalamic-pituitary-adrenal axis and other endocrine systems.
Speert
Debra B
DB
Neuroscience Graduate Program, Mental Health Research Institute, Ann Arbor, Michigan 48109-0720, USA.
MCClennen
Shanna J
SJ
Seasholtz
Audrey F
AF
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D004031:Diestrus; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D030762:Estrous Cycle; D005260:Female; D015870:Gene Expression; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010052:Ovariectomy; D010902:Pituitary Gland / Q000737:chemistry / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000032:analysis; D011359:Proestrus; D011388:Prolactin / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D012727:Sex Characteristics
D002352:Carrier Proteins; D012333:RNA, Messenger; C067133:corticotropin releasing factor-binding protein; C074283:estradiol 3-benzoate; D004958:Estradiol; D011333:Pro-Opiomelanocortin; D011388:Prolactin