Impaired estrogen feedback and infertility in female mice with pituitary-specific deletion of estrogen receptor alpha (ESR1).
Mice lacking estrogen receptor alpha in the pituitary gonadotroph (PitEsr1KO) were generated to determine the physiologic role of pituitary estrogen signaling in the reproductive axis. PitEsr1KO female mice are subfertile or infertile and have elevated levels of serum luteinizing hormone (LH) and LH beta subunit gene expression, reflecting a lack of estrogen negative feedback effect on the gonadotroph. While serum LH values are elevated in PitEsr1KO mice, the degree of elevation is much less than that observed in ESR1-null mice, indicating that the hypothalamus must also have an important role in estrogen negative feedback. PitEsr1KO mice also demonstrate a defect in estrogen positive feedback, as surge LH values and estrous cyclicity are absent in these mice. Although sex steroid feedback in the reproductive axis is thought to involve discrete anatomic regions that mediate either a positive or negative estrogen effect, PitEsr1KO mice demonstrate novel evidence that localizes both estrogen positive feedback and estrogen negative feedback to the gonadotroph, which suggests that they may be mechanistically related.
Singh
Surya P
SP
Divisions of Pediatric Endocrinology and Metabolism, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
Wolfe
Andrew
A
Ng
Yewade
Y
DiVall
Sara A
SA
Buggs
Colleen
C
Levine
Jon E
JE
Wondisford
Fredric E
FE
Radovick
Sally
S
D000818:Animals; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism; D004967:Estrogens / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D030762:Estrous Cycle / Q000097:blood / Q000235:genetics; D025461:Feedback, Physiological / Q000187:drug effects / Q000502:physiology*; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood; D007247:Infertility, Female / Q000097:blood / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D007986:Luteinizing Hormone / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009928:Organ Specificity / Q000235:genetics; D010053:Ovary / Q000378:metabolism / Q000473:pathology; D010902:Pituitary Gland / Q000378:metabolism*
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D012739:Gonadal Steroid Hormones; D007986:Luteinizing Hormone