title: Cell-specific induction of c-fos expression in the pituitary gland by estrogen.
abstract: Estrogens regulate many functions of pituitary lactotrophs, including PRL gene expression, release, storage, and cellular proliferation. The mechanism by which estrogens exert such a variety of functions is poorly understood. In the uterus, estrogens rapidly and transiently induce the expression of the immediate early genes c-fos and c-jun in specific cell types. The Fos/Jun proteins form the activating protein-1 (AP1) transcription factor that mediates ligand-activated cell proliferation, differentiation, and secretion. Here we used Fischer 344 (F344) rats that develop hyperprolactinemia and prolactinomas in response to estrogens. The objectives were to: 1) determine whether estrogen induces c-fos expression in the pituitary gland and identify the responsive cells; 2) compare the dynamics of c-fos induction in the pituitary and uterus; and 3) examine the temporal relationship between c-fos expression and PRL release. Ovariectomized F344 rats were injected with 1 microg estradiol and killed at different times thereafter. Pituitaries were subjected to in situ hybridization for c-fos and immunostaining for selected pituitary cells. Estradiol stimulated c-fos expression in lactotrophs and folliculo-stellate cells within the anterior lobe without affecting either the intermediate or neural lobes. In a second experiment, c-fos messenger RNA levels were measured by solution hybridization in anterior pituitaries and uteri from estradiol-treated rats. Trunk blood was analyzed for PRL by RIA. The estrogen-induced c-fos rise in the uterus was rapid, robust, and transient, whereas that in the anterior pituitary was delayed, lower, and sustained. The profile of serum PRL levels resembles that of c-fos induction in the anterior pituitary. We conclude that: 1) both lactotrophs and folliculo-stellate cells increase c-fos expression in response to estrogens; 2) induction of c-fos expression may mediate some estrogenic effects on PRL synthesis and release and lactotroph proliferation in F344 rats; and 3) the atypical dynamics of c-fos induction in the pituitary could be due to indirect effects of estrogens on PRL-regulating factors within the hypothalamo-pituitary complex as well as to pituitary-specific estrogen receptor isoforms, coactivators, or repressors.
authors.affiliation: Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati School of Medicine, Ohio 45267-0521, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Allen
authors.forename: N A
authors.initials: NA
authors.lastname: Mitchner
authors.forename: T E
authors.initials: TE
authors.lastname: Uveges
authors.forename: K P
authors.initials: KP
authors.lastname: Nephew
authors.forename: S
authors.initials: S
authors.lastname: Khan
authors.forename: N
authors.initials: N
authors.lastname: Ben-Jonathan
mesh_terms: D000818:Animals; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D016762:Genes, fos / Q000235:genetics*; D017403:In Situ Hybridization; D007700:Kinetics; D010052:Ovariectomy; D010902:Pituitary Gland / Q000378:metabolism*; D010903:Pituitary Gland, Anterior / Q000378:metabolism; D011388:Prolactin / Q000097:blood / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D014599:Uterus / Q000378:metabolism
chemical_list: D004958:Estradiol; D011388:Prolactin