The role of lipoproteins in the regulation of progesterone secretion by the human corpus luteum

Bruce R. Carr, Paul C. Macdonald, Evan R. Simpson

Research output: Contribution to journalArticlepeer-review


The human corpus luteum secretes as much as 40 mg of progesterone per day during the midluteal phase of the ovarian cycle. It is recognized that the secretion of progesterone is the property primarily of the luteinized granulosa cells of the corpus luteum, whereas the granulosa cells of the follicle secrete far smaller quantities of the hormone. The commencement of progesterone secretion by the corpus luteum is generally believed to be regulated by luteinizing hormone (LH) and to follow the surge of LH that occurs just before ovulation. The granulosa cells secrete relatively small quantities of progesterone during the follicular phase of the ovarian cycle. One possible explanation for this is the presence of inhibitory factors in follicular fluid. A number of substances have been found to inhibit luteinization and progesterone secretion by granulosa cells. Among these is high-density lipoprotein (HDL), which may inhibit or reduce progesterone secretion by follicular cells by promoting cholesterol efflux from such cells. In the present discussion, the authors present evidence that yet another factor may be of critical importance in determining the rate of progesterone secretion by various cells of the ovary throughout the ovarian cycle. This factor is cholesterol in the form of plasma lipoprotein and, in particular, low-density lipoprotein (LDL). Progesterone secretion by luteinized cells is stimulated principally by LH. The fact that LH does not stimulate progesterone biosynthesis in granulosa cells that are present in ovarian folliclesin vivo is believed to be due to the absence of LH receptors on such cells until late in the follicular phase. These cells do, however, contain receptors for FSH, which should stimulate the production of progesterone. The possibility was entertained that granulosa cells stimulated by FSH do not secrete large quantities of progesterone because of the lack of a precursor for progesterone biosynthesis. The precursor of progesterone biosynthesis is cholesterol. Unesterified cholesterol, derived from the uptake and degradation of LDL, is believed to be involved in a number of key regulatory mechanisms within the cell. In studies of the regulation of steroid hormone biosynthesis in the human corpus luteum, it was observed that LDL, rather than high-density lipoprotein, was required for optimum rates of biosynthesis. It has been found recently that, whereas HDL is present in follicular fluid in reasonable quantities, the LDL content of the fluid is extremely low. The enzymatic capacity to synthesize progesterone is present in the granulosa cells within the follicle. The hormonal machinery to stimulate progesterone biosynthesis, namely, FSH receptors coupled to adenylate cyclase, is also present in these cells. One reason that large quantities of progesterone are not secreted by granulosa cells within the follicle is that cholesterol cannot be supplied in adequate quantities to serve as a precursor. This is caused by the lack of LDL within the ovarian follicular fluid, due to the fact that there is no blood supply to these cells. LH receptors in the granulosa cells in the dominant follicle are acquired in response to the action of FSH and estrogen. Subsequent to ovulation, luteinization occurs in such cells, and the ability to synthesize progesterone is acquired. The authors suggest that the ability to synthesize progesterone is not conferred upon the cells by the action of LH on cholesterol side-chain cleavage alone. The reason that progesterone is synthesized in large quantities in response to LH is that with ovulation, the luteinized cells are then exposed to ample quantities of LDL, the cholesterol of which serves as the precursor for progesterone biosynthesis. After ovulation, vascularization of the luteinized granulosa cells occurs, and these cells, during the luteal phase of the cycle, are exposed to LDL in concentrations similar to those present in plasma.

Original languageEnglish (US)
Pages (from-to)216-217
Number of pages2
JournalObstetrical and Gynecological Survey
Issue number4
StatePublished - 1983

ASJC Scopus subject areas

  • Obstetrics and Gynecology


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