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Estradiol attenuates prolactin secretion and phosphoinositide hydrolysis in MMQ cells
T Kubota1, I S Login, A M Judd
1Department of Internal Medicine, University of Virginia Health Sciences Center, Charlottesville 22908.
Abstract:
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)
Insights
Tumor cells secreting prolactin (PRL) gained responsiveness to secretagogues after in vivo propagation. However, 17 beta-estradiol treatment attenuated this response, impacting PRL release and cellular mechanisms.
Area of Science:
- Endocrinology
- Cell Biology
- Oncology
Background:
- A clonal cell line, MMQ, was previously isolated for its exclusive prolactin (PRL) secretion.
- This cell line demonstrated nonresponsiveness to thyrotropin-releasing hormone (TRH) and angiotensin II (AII).
Purpose of the Study:
- To investigate if MMQ cells regain secretagogue responsiveness after in vivo propagation.
- To determine the effects of 17 beta-estradiol on PRL release and intracellular mechanisms in MMQ cells.
Main Methods:
- MMQ cells were implanted subcutaneously in female rats, with one group receiving polyestradiol phosphate (PEP) and the other saline.
- Tumor-derived cells (MMQt) were enzymatically dispersed and perifused in vitro to assess PRL release.
- Responses to TRH, AII, and maitotoxin (MTX) were measured in both control and PEP-treated MMQt cells.
Main Results:
- In vitro propagated MMQt cells showed increased PRL release in response to TRH, AII, and MTX.
- In vivo administration of PEP did not alter basal PRL release but significantly attenuated the responses to TRH, AII, and MTX.
Conclusions:
- In vivo propagation can restore secretagogue responsiveness in MMQ cells.
- 17 beta-estradiol administration in vivo significantly inhibits the responsiveness of MMQ cells to PRL secretagogues.