Modulation by insulin of follicle-stimulating hormone and luteinizing hormone actions in human granulosa cells of normal and polycystic ovaries

Willis, Debbie

doi:10.1210/jc.81.1.302

Cited by 167 publications

(104 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Anovulatory PCOS patients have a greater BMI than their ovulatory sisters despite a similar degree of ovarian hyperandrogenism [62], and weight loss in obese PCOS patients reverses anovulatory infertility [63]. Since insulin enhances FSHinduced upregulation of LH receptors in granulosa cells and increases their progesterone (P4) responsiveness to LH [64,65], hyperinsulinemia presumably induces premature follicle luteinization, which arrests cell proliferation and follicle growth. Consequently small antral PCOS follicles exhibit P4 hypersecretion and overexpress LH receptors [66,67], causing an exaggerated steroidogenic shift from E2 to P4 production [68].…”

Section: Impaired Follicle Growthmentioning

confidence: 99%

Polycystic ovary syndrome and its developmental origins

Dumesic

Abbott

Padmanabhan

2007

Rev Endocr Metab Disord

254

168

View full text Add to dashboard Cite

The prenatal testosterone (T)-treated adult female rhesus monkey is one animal model of polycystic ovary syndrome (PCOS) in women, with early prenatal T excess programming a permanent PCOS-like phenotype characterized by luteinizing hormone (LH) hypersecretion from reduced hypothalamic sensitivity to steroid negative feedback and relative insulin excess from increased abdominal adiposity. These combined reproductive and metabolic abnormalities are associated with ovarian hyperandrogenism and follicular arrest in adulthood, as well as premature follicle differentiation and impaired embryo development during gonadotropin therapy for in vitro fertilization (IVF). A second animal model for PCOS, the prenatal T-treated sheep also is characterized by LH hypersecretion from reduced hypothalamic sensitivity to steroid negative feedback, persistent follicles and insulin resistance, but also is associated with intrauterine growth retardation and compensatory growth after birth. The ability of prenatal T excess in both species to alter the developmental trajectory of multiple organ systems in utero provides evidence that the hormonal environment of intrauterine life programs target tissue differentiation, raising the possibility that T excess in human fetal development promotes PCOS in adulthood. Such a hypothesis must include data from clinical studies of PCOS women to clarify the homology between these PCOS-like animal models and PCOS per se in reproductive and metabolic function. Future studies should develop new clinical strategies that improve pregnancy outcome and minimize pregnancy loss in women with disorders of insulin action, including PCOS, obesity and diabetes mellitus as well as minimize transgenerational susceptibility to adult PCOS and its metabolic derangements in male close relatives.

show abstract

Section: Impaired Follicle Growthmentioning

confidence: 99%

Polycystic ovary syndrome and its developmental origins

Dumesic

Abbott

Padmanabhan

2007

Rev Endocr Metab Disord

254

168

View full text Add to dashboard Cite

show abstract

“…Insulin receptors are also expressed in granulosa cells, where they play a role in potentiating FSH-stimulated steroid secretion, as shown by increased estrogen secretion by granulosa cells exposed simultaneously to insulin and FSH [18]. In addition, the gonadotropic effect of insulin on folliculogenesis enhances the recruitment and growth of pre-ovulatory follicles [16], decreases the apoptosis and atresia of ovarian follicles [19], and stimulates the passage from primordial to primary follicles [20].…”

Section: Ovarian Function In T1d (Fig 1)mentioning

confidence: 99%

Puberty and Ovarian Function in Girls with Type 1 Diabetes Mellitus

Codner

Cassorla

2008

Horm Res Paediatr

View full text Add to dashboard Cite

Insulin is well known for its effects on carbohydrate metabolism, but this hormone also plays an important role in regulating ovarian function. Granulosa, theca and stromal ovarian cells may be affected by insulin deficiency or excess, which may be present in women with type 1 diabetes mellitus (T1D). Recent publications have shown that in spite of intensive insulin therapy, some delay in the age of thelarche, pubarche and menarche is still observed in girls with T1D. In addition, ovarian hyperandrogenism may be observed during late adolescence and an increased prevalence of hirsutism and polycystic ovarian syndrome (PCOS) has been described in adult women with T1D. These endocrine abnormalities may be related to nonphysiologic insulin replacement therapy and to hyperglycemia. This paper reviews the pubertal development and the clinical reproductive abnormalities observed in girls with type 1 diabetes mellitus, and shows that several significant clinical problems, such as pubertal delay, menstrual disturbances and hyperandrogenism which may ultimately lead to the development of PCOS in adulthood, may be observed in some of these patients.

show abstract

“…In women with T1DM, the aetiology of their hyperandrogenism is unclear, and it has been proposed that their hyperandrogenism is due to non-physiological insulin replacement therapy (4,5). Indeed, the results of several laboratory and clinical studies have found that insulin can also influence the production of ovarian and adrenal androgens (6,7,8,9,10,11).…”

Section: Introductionmentioning

confidence: 99%

High prevalence of hirsutism and menstrual disorders in obese adolescent girls and adolescent girls with type 1 diabetes mellitus despite different hormonal profiles

Samara-Boustani

Colmenares

Elie

et al. 2012

European Journal of Endocrinology

View full text Add to dashboard Cite

Objectives: To compare the pubertal development, the hormonal profiles and the prevalence of hirsutism and menstrual disorders in obese adolescent girls and adolescent girls with type 1 diabetes mellitus (T1DM). Methods: Data were collected from 96 obese adolescent girls and 78 adolescent girls with T1DM at Tanner stage IV or V, whose ages ranged between 11.9 and 17.9 years. Results: High prevalence of hirsutism and menstrual disorder was found in the obese adolescent girls (36.5 and 42% respectively) and the adolescent girls with T1DM (21 and 44% respectively). The obese girls were significantly younger at pubarche, thelarche and menarche than the girls with T1DM. Hirsutism in the obese girls and those with T1DM was associated with hyperandrogenaemia and a raised free androgen index (FAI). When the cause of the raised FAI was investigated in both the groups of girls with hirsutism, the raised FAI in the obese girls was due to low serum sex hormone-binding globulin (SHBG) levels. In contrast, the raised FAI of the girls with T1DM and hirsutism was due to hyperandrogenaemia. Menstrual disorders in the T1DM girls were associated also with hyperandrogenaemia unlike obese girls. Conclusions: Hirsutism and menstrual disorders are common in obese adolescent girls and adolescent girls with T1DM. Although hyperandrogenaemia is present in both groups of girls, the androgenic profiles of the two groups differ. The hyperandrogenaemia in the obese girls is primarily due to their decreased serum SHBG levels, whereas the hyperandrogenaemia in the girls with T1DM is due to their increased androgen production.

show abstract

Modulation by insulin of follicle-stimulating hormone and luteinizing hormone actions in human granulosa cells of normal and polycystic ovaries

Cited by 167 publications

References 0 publications

Polycystic ovary syndrome and its developmental origins

Polycystic ovary syndrome and its developmental origins

Puberty and Ovarian Function in Girls with Type 1 Diabetes Mellitus

High prevalence of hirsutism and menstrual disorders in obese adolescent girls and adolescent girls with type 1 diabetes mellitus despite different hormonal profiles

Contact Info

Product

Resources

About