Journal of Clinical Endocrinology & Metabolism, Vol 77, 188-194, Copyright © 1993 by Endocrine Society

ARTICLES

Regulation of parathyroid hormone-related protein gene expression in human endometrial stromal cells in culture

ML Casey, M Mibe and PC MacDonald
Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas 75235-9051.

The regulation of PTH-related protein (PTH-rP) gene expression by human endometrial stromal cells in monolayer culture was evaluated. 17 beta- Estradiol (E2), interleukin-1 beta (IL-1 beta), tumor necrosis factor- alpha (TNF alpha), endothelin-1 (ET-1), transforming growth factor-beta 1 (TGF beta 1), and serum stimulated PTH-rP production (evaluated by immunoassay of PTH-rP in the culture medium) by these cells. Treatment of endometrial stromal cells with E2 plus a progestin, medroxy- progesterone acetate (MPA), caused a decrease in PTH-rP production. PRL, epidermal growth factor, and dexamethasone, which are known to affect PTH-rP production (increase or decrease) in other cells, were ineffective in altering PTH-rP production in endometrial stromal cells, as were a number of other growth factors, viz. TGF alpha, platelet- derived growth factor, and basic fibroblast growth factor, and metabolites of progesterone. The effects of E2 and MPA on PTH-rP gene expression in these cells were investigated in detail. E2 (50 nM) increased PTH-rP mRNA levels (at 2, 4, 8, 12, and 24 h). When serum (10%) was present in the medium, E2 (50 nM) did not increase PTH-rP production or PTH-rP mRNA levels, and in the presence of serum, E2 plus MPA did not decrease PTH-rP production. In cells that were pretreated with E2 (50 nM) for 48 h before treatment (18 h) with ET-1, TNF alpha, tetradecanoylphorbol acetate, and TGF beta 1, the production of PTH-rP was greater than that in cells not pretreated with estrogen. The effect of treatment of endometrial stromal cells with MPA on PTH-rP mRNA levels (at 2, 4, 8, and 12 h) was variable, but in all studies conducted, PTH-rP production after 18 or 24 h of progestin treatment was not increased compared with that in nontreated cells. We conclude that estrogen acts directly in endometrial stroma cells to increase PTH- rP mRNA levels and PTH-rP protein production. In addition IL-1 beta, TNF alpha, ET-1, TGF beta 1, and serum stimulate PTH-rP production by these cells. With the exception of serum, the effects of most of the other agents identified in this study to stimulate PTH-rP production were at least additive with that of E2.

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