Estradiol attenuates prolactin secretion and phosphoinositide hydrolysis in MMQ cells.
We previously isolated a clonal cell line, designated MMQ, which only secretes prolactin (PRL) and whose secretory process is nonresponsive to thyrotropin releasing hormone (TRH) and angiotensin II (AII). In the present study, we injected MMQ cells into rats to determine whether the tumor cells would become responsive to secretagogues when subsequently propagated in vitro. We also investigated what effects in vivo administration of 17 beta-estradiol would have on secretagogue-induced PRL release and on intracellular biochemical mechanisms in these cells. MMQ cells were implanted subcutaneously in the backs of female rats. One group was injected with 100 micrograms polyestradiol phosphate (PEP) every 5 days, a second with saline. The inoculants grew into solid tumors within 3 weeks. The day after the tumors were removed and enzymatically dispersed, the cells, now designated MMQt cells, were perifused in vitro. Basal PRL released by MMQt cells was approximately 1 ng/min/10(7) cells and perifusions with 100 nM TRH or AII for 5 min significantly increased PRL release above baseline (integrated areas: 1.8 +/- 0.4 and 5.2 +/- 1.3 ng/10(7) cell, respectively; P less than 0.01). Two ng/ml maitotoxin (MTX), a calcium channel activator, increased PRL release (38.2 +/- 6.7 ng/10(7) cells; P less than 0.01). In PEP-treated perifused MMQt cells, basal in vitro PRL release was not different from that observed in the control group, but the responses to TRH, AII and MTX were greatly attenuated (TRH: 0.6 +/- 0.1, AII: 1.3 +/- 0.2 and MTX: 9.2 +/- 2.5 ng/10(7) cells).(ABSTRACT TRUNCATED AT 250 WORDS)
Kubota
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Department of Internal Medicine, University of Virginia Health Sciences Center, Charlottesville 22908.
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Judd
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Kuan
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MacLeod
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D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D045166:Estradiol Congeners / Q000494:pharmacology; D006868:Hydrolysis; D007295:Inositol Phosphates / Q000378:metabolism; D009496:Neurotensin / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D010477:Perfusion; D010716:Phosphatidylinositols / Q000378:metabolism*; D010902:Pituitary Gland / Q000187:drug effects; D011388:Prolactin / Q000032:analysis / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D011915:Rats, Inbred BUF; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D015259:Dopamine Agents; D045166:Estradiol Congeners; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D000804:Angiotensin II; D009496:Neurotensin; D004958:Estradiol; D013973:Thyrotropin-Releasing Hormone; D011388:Prolactin; C008958:polyestradiol phosphate; D002118:Calcium