GLYCOPROTEIN HORMONE ALPHA-SUBUNIT FUNCTIONS SYNERGISTICALLY WITH PROGESTERONE TO STIMULATE DIFFERENTIATION OF CULTURED HUMAN ENDOMETRIAL STROMAL CELLS TO DECIDUALIZED CELLS - A NOVEL ROLE FOR FREE ALPHA-SUBUNIT IN REPRODUCTION

Glycoprotein hormone-free alpha subunit is secreted by the pituitary t hroughout the menstrual cycle and by the placenta during pregnancy. We showed previously that free a subunit stimulated PRL secretion from t erm pregnancy decidual cells, suggesting a function for free alpha in pregnancy. However, no role has been ascribed to free alpha in the nor mal menstrual cycle. Using an in vitro model, we examined the role of alpha subunit in regulating human endometrial stromal cell differentia tion (decidualization). PRL and insulin-like growth factor binding pro tein-1 (IGFBP-1), specific decidual secretory products, were used as m arkers of decidualization. We found that alpha subunit acted synergist ically with progesterone (P) to induce more rapid decidualization with higher output (2- to 6-fold) of PRL and IGFBP-1, compared with P alon e (P < 0.01). The effect of a was dose dependent, with stimulatory act ivity starting at 0.05 ng/ml and reaching maximal levels at 1-2 ng/ml. These levels correspond to serum concentrations of free alpha found d uring the luteal phase of the menstrual cycle when endometrial decidua lization occurs in vivo. These findings demonstrate new biological act ivity for a subunit in the regulation of human endometrial decidualiza tion and indicate that free alpha plays a role in human reproduction. Furthermore, demonstration of potential bioactivities of free a subuni t has important implications for understanding normal endocrine functi on and various pathological conditions.