Localization of Androgen Receptor in the Follicle and Corpus Luteum of the Primate Ovary during the Menstrual Cycle1

Hild-Petito, Sheri; West, Neal B.; Brenner, Robert; Stouffer, Richard L.

doi:10.1095/biolreprod44.3.561

Cited by 90 publications

(46 citation statements)

References 27 publications

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“…This effect may not be specific to progestin since androgen replacement was also associated with increased progesterone production in some animals. Immunocytochemical evidence for androgen receptors in the macaque (39) and human (40) corpus luteum support a function for androgens in luteal development and/or function. Furthermore, the duration of progesterone inhibition during the gonadotropin surge may have differential effects on subsequent luteal development.…”

Section: Discussionmentioning

confidence: 89%

Midcycle administration of a progesterone synthesis inhibitor prevents ovulation in primates.

Hibbert

Stouffer

Wolf

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

126

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Progesterone receptors appear in granulosa cells of preovulatory follicles after the midcycle gonadotropin surge, suggesting important local actions of progesterone during ovulation in primates. Steroid reduction and replacement during the gonadotropin surge in macaques was used to evaluate the role of progesterone in the ovulatory process. Animals received gonadotropins to induce development of multiple preovulatory follicles, followed by human chorionic gonadotropin (hCG) administration (day 0) to promote oocyte (nuclear) maturation, ovulation, and follicular luteinization. On days 0-2, animals received no further treatment; a steroid synthesis inhibitor, trilostane (TRL); TRL + R5020; or TRL + dihydrotestosterone propionate (DHT). On day 3, ovulation was confirmed by counting ovulation sites and collecting oviductal oocytes. The meiotic status of oviductal and remaining follicular oocytes was evaluated. Peak serum estradiol levels, the total number of large follicles, and baseline serum progesterone levels at the time of hCG administration were similar in all animals. Ovulation sites and oviductal oocytes were routinely observed in controls. Ovulation was abolished in TRL. Progestin, but not androgen, replacement restored ovulation. Relative to controls, progesterone production was impaired for the first 6 days post-hCG in TRL, TRL + R5020, and TRL + DHT. Thereafter, progesterone remained low in TRL but recovered to control levels with progestin and androgen replacement. Similar percentages of mature (metaphase II) oocytes were collected among groups. Thus, steroid reduction during the gonadotropin surge inhibited ovulation and luteinization, but not reinitiation of oocyte meiotic maturation, in the primate follicle. The data are consistent with a local receptor-mediated role for progesterone in the ovulatory process.A hallmark of reproductive cycles in female mammals is the process of ovulation. A triad of well-coordinated events occurs locally within the ovarian follicle during the periovulatory interval. First, the follicle-enclosed oocyte undergoes both nuclear and cytoplasmic maturation to render it capable of fertilization. Second, the mature, preovulatory follicle ruptures-i.e., ovulates-to release the oocyte. Third, luteinization of the steroidogenic somatic cells of the follicle, known as theca and granulosa cells, results in morphological differentiation to form the corpus luteum. The ovulatory process is initiated by the surge of pituitary gonadotropins, mainly luteinizing hormone (LH), that occurs at midcycle (1). Other factors produced within the follicle during the periovulatory period, such as metabolites of arachidonic acid (2), peptides (3), and steroids (4), likely play a role in LH-induced ovulation, at least in rodent models. Understanding the ovulatory process is obligatory for development of therapies to alleviate infertility due to ovulatory dysfunction, such as the luteinizing unruptured follicle syndrome (5) in women, as well as alternative methods for controlling fertility by...

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Section: Discussionmentioning

confidence: 89%

Midcycle administration of a progesterone synthesis inhibitor prevents ovulation in primates.

Hibbert

Stouffer

Wolf

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

126

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“…These results suggest a progestational rather than an estrogenic regulation of ovarian function in the monkey. Hild-Petito et al (1991) have also demon-strated the presence of androgen receptors in the granulosa and theca cells of growing monkey follicles, and a paracrinelautocrine function has been ascribed to follicular androgen and its receptors. Iwai et al (1990) have shown immunocytochemically that human granulosa cells possess only estrogen receptors before the preovulatory LH surge; however, estrogen receptors disappear and progesterone receptors appear following the LH surge.…”

Section: Morphological Studies On Follicular Dna Synthesismentioning

confidence: 97%

Regulation of ovarian follicular development: A review of microscopic studies

Roy

1994

Microscopy Res & Technique

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Follicular development in the mammalian ovary is a complex process regulated by an orchestrated action of the pituitary gonadotropins, e.g., follicle stimulating hormone (FSH) and luteinizing hormone (LH), and local ovarian factors, such as peptide growth factors and steroids. The mechanism of endocrine/paracrine/autocrine regulation of folliculogenesis (i.e., cell proliferation and functions) has been addressed largely by biochemical means. However, the availability of immunological and molecular tools now enables us to undertake critical microscopic studies revealing the ovarian cell-type specific synthesis and/or accumulation of many of these local peptide modulators, their roles in the proliferation and differentiation of follicular cells, and their regulation by gonadotropins and local factors. The objective of this review is to provide a comprehensive yet complete picture of the endocrine/autocrine regulation of mammalian folliculogenesis as revealed by microscopic studies. Efforts have been made to include adequate research information relevant to update our understanding of the process of follicular development; however, to maintain the brevity, many equally important studies could not be included. This review confirms that FSH and LH are still the primary stimuli for follicular development. However, it is clear that the actions of these hormones at the cell level involve a host of peptide factors which are produced locally by different follicular cell types and which are powerful modulators of gonadotropin actions. The temporal and spatial expression of the genes of these modulators, the synthesis of active factors, their interactions, and the dynamics of their receptors on the follicular cell surface may be the ultimate determinants of cellular events which are crucial to coordinated growth and differentiation of follicular cells leading to folliculogenesis and ovulation.

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“…However, the modulation of AR expression by follicular development has not been observed in monkeys (7) and women (8), presumably because of methodological differences (5). Incidentally, in these two latter species, ARs have been detected both in granulosa and thecal cells (7,8).…”

Section: Androgens and Folliculogenesis: Physiologic Bases And Animalmentioning

confidence: 99%

Androgens and poor responders: are we ready to take the plunge into clinical therapy?

Fanchin

Frydman

Even

et al. 2011

Fertility and Sterility

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Localization of Androgen Receptor in the Follicle and Corpus Luteum of the Primate Ovary during the Menstrual Cycle1

Cited by 90 publications

References 27 publications

Midcycle administration of a progesterone synthesis inhibitor prevents ovulation in primates.

Midcycle administration of a progesterone synthesis inhibitor prevents ovulation in primates.

Regulation of ovarian follicular development: A review of microscopic studies

Androgens and poor responders: are we ready to take the plunge into clinical therapy?

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