Functional and morphological differentiation of theca and granulosa cells during pregnancy in the rat: Dependence on increased basal luteinizing hormone activity

Abstract

In order to examine the possibility that development of ovulatory follicles is primarily dependent upon LH (hCG)-induced differentiation of theca cells, the morphology and steroidogenic activity of thecae isolated from small antral follicles on day 16 of pregnancy has been compared to that of thecae isolated from preovulatory follicles that develop in response to either increased endogenous levels of LH at the end of pregnancy or to subovulatory doses of hCG administered to rats on days 14 and 15 of pregnancy. Light and electron micrographs indicate that theca cells of small antral follicles were condensed toward the basement membrane and were devoid of any morphological features characteristic of steroidogenically active cells. In contrast, theca interna cells of preovulatory follicles isolated either on day 23 of pregnancy or after treatment with 1.5 IU hCG on the morning and evening of days 14 and 15 were hypertrophied and contained increased amounts of lipid and an extensive smooth endoplasmic reticulum. This suggested that increased steroidogenic activity of theca interna cells followed exposure to increased LH activity in vivo. Production of both testosterone (T) and estradiol by small antral follicles was minimal and generally less than 10 pg/follicle · 5 h. Follicles exposed to 1.0 IU of hCG in vivo for 12 h or longer on days 14 and 15 of pregnancy produced significantly greater amounts of each steroid, which at 60 h were maximal [1604.5 ± 233.4 pg T/follicle-5 h; 1266.9 ± 171.6 pg estradiol/follicle · 5 h (mean ± SEM]. These amounts were similar to those produced by preovulatory follicles isolated on day 23 of pregnancy. As was the case with intact follicles, individual thecae isolated on day 16 of pregnancy produced minimal testosterone (16.9 ± 4.0 pg/theca-5 h), whereas testosterone production by thecae exposed to hCG in vivo (0.25-2.50 IU) increased in a dosedependent manner, and attained a maximum of 175.4 ± 39.9 pg T/theca-5 h. The addition of progesterone (100 ng/ml) to the incubation media enhanced testosterone production by isolated thecae in all instances, and suggested that LH (hCG) may stimulate the conversion of progesterone to testosterone by theca cells. Since similar studies of isolated granulosa cells indicated that maximal aromatase activity was present even in small antral follicles, increased estradiol production by antral follicles results directly from increased androgen production by theca interna cells. Furthermore, we conclude that functional differentiation of theca interna cells is dependent primarily upon modest increases in basal LH activity and occurs in the presence of elevated levels of serum progesterone. © 1981 by The Endocrine Society.