Serum α-Inhibin Levels in Polycystic Ovary Syndrome: Relationship to the Serum Androstenedione Level1

Pigny, Pascal; Desailloud, Rachel; Cortet‐Rudelli, Christine; Duhamel, Alain; Deroubaix-Allard, Delphine; Racadot, A; Dewailly, Didier

doi:10.1210/jcem.82.6.4015

Cited by 15 publications

(1 citation statement)

References 45 publications

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“…Investigators have also examined inhibin levels in women with polycystic ovary syndrome (PCOS), in whom there is relative FSH suppression compared with LH. Serum inhibin a subunit, inhibin-A, and inhibin-B levels in PCOS women were comparable with early follicular phase levels in normal cycling women (26,37,38) or were increased (39)(40)(41). Furthermore, inhibin subunit mRNA levels were lower in the granulosa cells of women with PCOS compared with normal granulosa cells from similarly sized follicles (42).…”

Section: Endocrine Roles Of Inhibin Activin and Fsmentioning

confidence: 80%

Activins, Inhibins, and Follistatins: From Endocrinology to Signaling. A Paradigm for the New Millennium

Welt

Sidis²,

Keutmann

et al. 2002

Exp Biol Med (Maywood)

293

275

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It has been 70 years since the name inhibin was used to describe a gonadal factor that negatively regulated pituitary hormone secretion. The majority of this period was required to achieve purification and definitive characterization of inhibin, an event closely followed by identification and characterization of activin and follistatin (FS). In contrast, the last 15–20 years saw a virtual explosion of information regarding the biochemistry, physiology, and biosynthesis of these proteins, as well as identification of activin receptors, and a unique mechanism for FS action—the nearly irreversible binding and neutralization of activin. Many of these discoveries have been previously summarized; therefore, this review will cover the period from the mid 1990s to present, with particular emphasis on emerging themes and recent advances. As the field has matured, recent efforts have focused more on human studies, so the endocrinology of inhibin, activin, and FS in the human is summarized first. Another area receiving significant recent attention is local actions of activin and its regulation by both FS and inhibin. Because activin and FS are produced in many tissues, we chose to focus on a few particular examples with the most extensive experimental support, the pituitary and the developing follicle, although nonreproductive actions of activin and FS are also discussed. At the cellular level, it now seems that activin acts largely as an autocrine and/or paracrine growth factor, similar to other members of the transforming growh factor β superfamily. As we discuss in the next section, its actions are regulated extracellularly by both inhibin and FS. In the final section, intracellular mediators and modulators of activin signaling are reviewed in detail. Many of these are shared with other transforming growh factor β superfamily members as well as unrelated molecules, and in a number of cases, their physiological relevance to activin signal propagation remains to be elucidated. Nevertheless, taken together, recent findings suggest that it may be more appropriate to consider a new paradigm for inhibin, activin, and FS in which activin signaling is regulated extracellularly by both inhibin and FS whereas a number of intracellular proteins act to modulate cellular responses to these activin signals. It is therefore the balance between activin and all of its modulators, rather than the actions of any one component, that determines the final biological outcome. As technology and model systems become more sophisticated in the next few years, it should become possible to test this concept directly to more clearly define the role of activin, inhibin, and FS in reproductive physiology.

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Section: Endocrine Roles Of Inhibin Activin and Fsmentioning

confidence: 80%

Activins, Inhibins, and Follistatins: From Endocrinology to Signaling. A Paradigm for the New Millennium

Welt

Sidis²,

Keutmann

et al. 2002

Exp Biol Med (Maywood)

293

275

View full text Add to dashboard Cite

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The pathogenesis of polycystic ovary syndrome: Lessons from ovarian stimulation studies

Barnes

1998

J Endocrinol Invest

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In polycystic ovary syndrome (PCOS) the ovary produces markedly increased amounts of both androgens and estrogens in response to gonadotropin stimulation. Distinctive responses of 17-hydroxyprogesterone and androstenedione to ovarian stimulation testing suggest that ovarian hyperandrogenism is a result of dysregulation of theca cell androgen production which is intrinsic to the ovary. The occurrence of hyperestrogenism together with hyperandrogenism in PCOS suggests that whatever the abnormality of local regulatory factors of steroidogenesis, it affects granulosa as well as theca cells. Dysregulation is often associated with an increase in the number of follicles which evade atresia and reach the 2-8 mm stage of development. Autocrine/paracrine factors, especially those which are FSH-dependent, likely play an important role in the pathogenesis of the ovarian abnormality. Both LH and insulin hypersecretion probably play a secondary role in PCOS by amplifying the preexisting ovarian dysregulation. Because FSH secretion is under tight long-loop negative-feedback control and LH is not, hyperandrogenism is the primary clinical manifestation of dysregulation of steroid production in PCOS. However, anovulation in PCOS is most likely a result of excessive estrogen and inhibin production by multiple, small follicles which inhibit FSH secretory dynamics sufficiently to prevent selection of a dominant follicle.

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Insights into hypothalamic-pituitary dysfunction in polycystic ovary syndrome

Hall

Taylor

Hayes

et al. 1998

J Endocrinol Invest

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Polycystic ovary syndrome (PCOS) is characterized by menstrual dysfunction and hyperandrogenism in the absence of other known causes. While the pathogenesis of PCOS remains elusive and is likely to involve abnormalities in several systems, there has long been an association of abnormal gonadotropin secretion with this disorder. In recent studies we have determined that 94% of women meeting the broad criteria for PCOS have an increased LH/FSH ratio. Several lines of evidence suggest that the mechanisms underlying the increased LH/FSH ratio in PCOS include an increased frequency of GnRH secretion. Decreased sensitivity to progesterone negative feedback on the GnRH pulse generator may play a role in this neuroendocrine defect. Additional factors which may contribute to the low to normal FSH levels in the face of increased LH include chronic mild estrogen increases and possibly inhibin. In addition to these effects on the differential control of FSH, there is increased pituitary sensitivity of LH secretion to GnRH. Both estrogen and androgens have been proposed as candidates mediating these effects. Superimposed on these underlying abnormalities in gonadotropin secretion is a marked inhibitory effect of obesity on LH secretion which may be mediated at either a pituitary or hypothalamic level.

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Serum α-Inhibin Levels in Polycystic Ovary Syndrome: Relationship to the Serum Androstenedione Level1

Cited by 15 publications

References 45 publications

Activins, Inhibins, and Follistatins: From Endocrinology to Signaling. A Paradigm for the New Millennium

Activins, Inhibins, and Follistatins: From Endocrinology to Signaling. A Paradigm for the New Millennium

The pathogenesis of polycystic ovary syndrome: Lessons from ovarian stimulation studies

Insights into hypothalamic-pituitary dysfunction in polycystic ovary syndrome

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