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Sex Steroids and Growth Factors Differentially Regulate the Growth and Differentiation of Cultured Human Endometrial Stromal Cells^*

Departments of Reproductive Biology (J.C.I., W.H.U., R.L.E.), Biochemistry (R.L.E.), and Physiology and Biophysics (R.L.E.), Case Western Reserve University School of Medicine Cleveland, Ohio 44106

Address requests for reprints to: Dr. Richard L. Eckert, Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, 2109 Adelbert Road, Cleveland, Ohio 44106.

Abstract

We have studied the interaction between growth factors and sex steroids in regulating human endometrial stromal cell growth and differentiation using an in vitro serumfree cell culture model system. None of the growth factors [epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), insulin, insulin-like growth factor-I (IGF-I), IGF-II, or platelet-derived growth factor] stimulated the growth of human endometrial stromal cells grown in progestin-free medium. However, the growth of progestin-treated cultures was dramatically increased by EGF, bFGF, or platelet-derived growth factor, but not by insulin, IGF-I, or IGF-II. Estrogen could not substitute for progesterone in this protocol, and coadministration of estrogen with progestin did not enhance the response over that to progesterone alone. In contrast to their positive effects on growth, only EGF, not bFGF, stimulated stromal cell differentiation, as measured by an increase in PRL, laminin, and fibronectin production; moreover, stimulation of differentiation was dependent upon the presence of progestin in the culture medium.

Thus, human endometrial stromal cell growth is 1) regulated by a discrete set of growth factors, only a subset of which regulates stromal cell differentiation; and 2) regulation of stromal cell growth and stromal cell differentiation by growth factors is progestin dependent. Our results provide direct evidence for interaction between growth factors and sex steroids in the regulation of stromal cell growth and differentiation in vitro and suggest that growth factors may be absolutely required in conjunction with progesterone for the decidual response in vivo. (Endocrinology 129: 2385–2392, 1991)

Footnotes

^* This work was supported by NIH Grant HD-25135 and used the facilities of the Skin Diseases Research Center of Northeast Ohio (Grant AR-39750).

Received May 21, 1991.

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