Cell-specific induction of c-fos expression in the pituitary gland by estrogen

D. L. Allen, N. A. Mitchner, T. E. Uveges, Kenneth Nephew, S. Khan, N. Ben-Jonathan

Research output: Contribution to journalArticle

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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 μg 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.

Original languageEnglish (US)
Pages (from-to)2128-2135
Number of pages8
JournalEndocrinology
Volume138
Issue number5
StatePublished - 1997
Externally publishedYes

Fingerprint

Pituitary Gland
Estrogens
Lactotrophs
Uterus
Inbred F344 Rats
Estradiol
Activating Transcription Factor 1
Cell Proliferation
Posterior Pituitary Gland
Prolactinoma
Hyperprolactinemia
Immediate-Early Genes
Estrogen Receptors
In Situ Hybridization
Cell Differentiation
Protein Isoforms
Proteins
Ligands
Gene Expression
Messenger RNA

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Allen, D. L., Mitchner, N. A., Uveges, T. E., Nephew, K., Khan, S., & Ben-Jonathan, N. (1997). Cell-specific induction of c-fos expression in the pituitary gland by estrogen. Endocrinology, 138(5), 2128-2135.

Cell-specific induction of c-fos expression in the pituitary gland by estrogen. / Allen, D. L.; Mitchner, N. A.; Uveges, T. E.; Nephew, Kenneth; Khan, S.; Ben-Jonathan, N.

In: Endocrinology, Vol. 138, No. 5, 1997, p. 2128-2135.

Research output: Contribution to journalArticle

Allen, DL, Mitchner, NA, Uveges, TE, Nephew, K, Khan, S & Ben-Jonathan, N 1997, 'Cell-specific induction of c-fos expression in the pituitary gland by estrogen', Endocrinology, vol. 138, no. 5, pp. 2128-2135.
Allen DL, Mitchner NA, Uveges TE, Nephew K, Khan S, Ben-Jonathan N. Cell-specific induction of c-fos expression in the pituitary gland by estrogen. Endocrinology. 1997;138(5):2128-2135.
Allen, D. L. ; Mitchner, N. A. ; Uveges, T. E. ; Nephew, Kenneth ; Khan, S. ; Ben-Jonathan, N. / Cell-specific induction of c-fos expression in the pituitary gland by estrogen. In: Endocrinology. 1997 ; Vol. 138, No. 5. pp. 2128-2135.
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