The Use of rLH, HMG and hCG in Controlled Ovarian Stimulation for Assisted Reproductive Technologies
UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD DEPT OF OBSTETRICS AND GYNECOLOGY
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The physiologic roles of both follicle stimulating hormone and luteinizing hormone are well established in the natural menstrual cycle. Research by Ryan and colleges in the 1960s established the concept of two different cells in the ovarian follicle, the thecal and granulosa cells, functioning in different manners to produce products of the steroid pathway, the two cell hypothesis 1, 2. Further work over the next two decades established the two-cell two-gonadotropin theory, demonstrating the action of FSH on granulosa cells and LH on thecal cells 3. Thecal cells alone were shown to express CYP17, the gene encoding for the critical enzyme in the conversion of progesterone and pregnenalone to androgens 3. Conversely, granulosa cells were demonstrated to be the cell expressing aromatase, allowing for the conversion of the androgens derived from the thecal cells to be converted to estrogens. The cooperation of both cells under the influence of both gonadotropins is essential for normal folliculogenesis and steroidogenesis in the ovary. LH has several physiologic roles within the ovary in addition to its roll in androgen production Figure 1. LH receptor activation leads to increases in adenylate cyclase and cAMP, resulting in increased mitochondrial transport of cholesterol necessary for steroidogeneis through upregulation of StAR 4, 5. LH activity also induces the expression of EGF-like growth factors amphiregulin and epiregulin from luteinized granulosa cells 6. These factors protect these cells from apoptosis, induce pro-survival signaling cascades, and are critical in peri-ovulatory events 6, 7. The mid-cycle LH surge causes a cascade of events leading to ovulation of the oocyte from the ovarian follicle and take the oocyte out of meiotic arrest 8. Finally, LH receptors have been demonstrated in the endometrium during the implantation window, raising a possible roll for LH in peri-implantation endometrial events 9, 10.
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