Formation of cystic ovarian follicles associated with elevated luteinizing hormone requires estrogen receptor-beta.
Stringent regulation of LH secretion from the pituitary is vital to ovarian function in mammals. Two rodent models of LH hypersecretion are the transgenic LHbeta-C-terminal peptide (LHbetaCTP) and estrogen receptor-alpha (ERalpha)-null (alphaERKO) mice. Both exhibit ovarian phenotypes of chronic anovulation, cystic and hemorrhagic follicles, lack of corpora lutea, interstitial/stromal hyperplasia, and elevated plasma estradiol and testosterone. Because ERbeta is highly expressed in granulosa cells of the ovary, we hypothesized the intraovarian actions of ERbeta may be necessary for full manifestation of phenotypes associated with LH hyperstimulation. To address this question, we generated female mice that possess elevated LH, but lack ERbeta, by breeding the LHbetaCTP and ERbeta-null (betaERKO) mice. A comparison of LHbetaCTP, alphaERKO, and betaERKO(LHCTP) females has allowed us to elucidate the contribution of each ER form to the pathologies and endocrinopathies that occur during chronic LH stimulation of the ovary. alphaERKO ovaries respond to elevated LH by exhibiting an amplified steroidogenic pathway characteristic of the follicular stage of the ovarian cycle, whereas wild-type(LHCTP) and betaERKO(LHCTP) females exhibit a steroidogenic profile more characteristic of the luteal stage. In addition, the hemorrhagic and cystic follicles of the LHbetaCTP and alphaERKO ovaries require the intraovarian actions of ERbeta for manifestation, because they were lacking in the betaERKO(LHCTP) ovary. In turn, ectopic expression of the Leydig cell-specific enzyme, Hsd17b3, and male-like testosterone synthesis in the alphaERKO ovary are unique to this genotype and are therefore the culmination of elevated LH and the loss of functional ERalpha within the ovary.
Couse
John F
JF
Receptor Biology Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, P.O. Box 12233, MD B3-02, Research Triangle Park, North Carolina 27709, USA.
Yates
Mariana M
MM
Sanford
Ryan
R
Nyska
Abraham
A
Nilson
John H
JH
Korach
Kenneth S
KS
D000818:Animals; D047629:Estrogen Receptor beta; D005260:Female; D015870:Gene Expression; D006728:Hormones / Q000097:blood; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010048:Ovarian Cysts / Q000097:blood / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D006080:Ovarian Follicle / Q000378:metabolism / Q000473:pathology; D010053:Ovary / Q000473:pathology; D011960:Receptors, Estrogen / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D047629:Estrogen Receptor beta; D006728:Hormones; D011960:Receptors, Estrogen; D007986:Luteinizing Hormone