Localization of steroidogenesis and steroid receptors in human corpus luteum. Classification of human corpus luteum (CL) into estrogen-producing degenerating CL, and nonsteroid-producing degenerating CL

Abstract

In the analysis of the regulation of human corpus luteum, it is very important to localize the sites of specific steroid hormone production to obtain a better understanding of luteal function. We have examined expression of steroidogenic enzymes, steroid receptors, and adrenal 4 binding protein (Ad4BP), a transcription factor of steroidogenesis, in corpus luteum of normal cycling human ovary. Corpus luteum can be classified into four different stages from ovulation to complete regression or fibrosis based on these findings: (1) corpus luteum, (2) steroid-producing degenerating corpus luteum or SPDCL, (3) nonsteroid producing or NSPDCL, and (4) corpus albicans. Corpus luteum in the luteal phase is characterized as follows: (a) the expression of P450scc (cholesterol side chain cleavage), 3 beta HSD (hydroxysteroid dehydrogenase), and Ad4BP in almost all the luteinized granulosa and theca cells, consistent with active progesterone biosynthesis; (b) expression of estrogen-producing P450arom (aromatase) in luteinized granulosa cells, indicating active estrogen production and that of P450c17 (17 alpha hydroxylase) in luteinized theca cells, and (c) expression of progesterone receptor (PR) and androgen receptor (AR) in both luteinized granulosa and theca cells. SPDCL correspond to corpus luteum undergoing regression or degeneration in the following cycle and are characterized as follows: (a) absence of all the steroidogenic enzymes and Ad4BP in the luteinized granulosa cells, suggestive of hormonally inactive nature of these cells and (b) marked expression of P450scc, 3 beta HSD, P450c17 and Ad4BP in luteinized theca cells. NSPDCL is characterized as the absence of all the steroidogenic enzymes and sporadic expression of Ad4BP in luteinized theca cells. These findings indicate that luteal cells remain even after losing expression of steroidogenic enzymes, consistent with a prolonged process of degeneration or regression of human corpus luteum. In corpus albicans, all the cells were replaced by fibrosis and steroidogenic enzymes; steroid receptors and Ad4BP were not expressed at all. Localization of steroidogenesis in human corpus luteum has thus provided new insights into understanding of its biological features.