Differential regulation by estrogens of growth and prolactin synthesis in pituitary cells suggests that only a small pool of estrogen receptors is required for growth.
PR1 cells are a prolactin (PRL)-secreting cell line derived from a pituitary lactotroph tumor found in 17beta-estradiol-treated Fischer 344 rats. We examined the effect of estrogen on cell proliferation and PRL synthesis under various culture conditions. Estrogen, at extremely low concentrations, induces cell proliferation in this cell line, whereas antiestrogen inhibits proliferation. Interestingly, the proliferation response is much more sensitive than the PRL response because 0.01 pM estradiol or diethylstilbestrol induces half-maximal growth induction [ approximately 0.1% estrogen receptor (ER) occupancy is required], whereas 0.01 nM concentration is required for half-maximal PRL induction ( approximately 50% ER occupancy is required). The proliferation response is not as sensitive to antiestrogen as the PRL response, because 10 nM concentration of the pure antiestrogen ICI 182,780 could not inhibit 1 nM estradiol- or diethylstilbestrol-induced proliferation. The same concentration of ICI 182,780 decreased PRL secretion to 1% of estradiol- or diethylstilbestrol-induced prolactin secretion suggesting a possible dichotomy of ER control of proliferation and PRL synthesis. The Kd of ER binding in these cells is about 3 x 10(-11) M. These results with the PR1 cells extend previous studies in other estrogen- regulated systems and suggest that only a small pool of ER is required for cell proliferation in contrast with the regulation of expression of specific genes. They also raise questions as to how a dimeric receptor functions when only one ligand site is occupied or when both an estrogen and an antiestrogen occupy one dimer.
Chun
T Y
TY
Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
Gregg
D
D
Sarkar
D K
DK
Gorski
J
J
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004054:Diethylstilbestrol / Q000494:pharmacology*; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D000077267:Fulvestrant; D007700:Kinetics; D010052:Ovariectomy; D010911:Pituitary Neoplasms / Q000139:chemically induced / Q000378:metabolism*; D011388:Prolactin / Q000096:biosynthesis*; D051381:Rats; D011916:Rats, Inbred F344; D011960:Receptors, Estrogen / Q000187:drug effects / Q000502:physiology*; D014407:Tumor Cells, Cultured
D004965:Estrogen Antagonists; D011960:Receptors, Estrogen; D000077267:Fulvestrant; D004958:Estradiol; D004054:Diethylstilbestrol; D011388:Prolactin