Enhanced thecal androgen production is prenatally programmed in an ovine model of polycystic ovary syndrome

Endocrinology. 2012 Jan;153(1):450-61. doi: 10.1210/en.2011-1607. Epub 2011 Nov 15.

Abstract

One of the hallmarks of polycystic ovary syndrome (PCOS) is increased ovarian androgen secretion that contributes to the ovarian, hormonal, and metabolic features of this condition. Thecal cells from women with PCOS have an enhanced capacity for androgen synthesis. To investigate whether this propensity is a potential cause, rather than a consequence, of PCOS, we used an ovine prenatal androgenization model of PCOS and assessed ewes at 11 months of age. Pregnant Scottish Greyface ewes were administered 100 mg testosterone propionate (TP) or vehicle control twice weekly from d 62 to 102 of gestation, and female offspring (TP = 9, control = 5) were studied. Prenatal TP exposure did not alter ovarian morphology or cyclicity, or plasma androgen, estrogen, and gonadotropin concentrations, at this stage. However, follicle function was reprogrammed in vivo with increased proportions of estrogenic follicles (P < 0.05) in the TP-exposed cohort. Furthermore, in vitro the thecal cells of follicles (>4 mm) secreted more LH-stimulated androstenedione after prenatal androgenization (P < 0.05), associated with increased basal expression of thecal StAR (P < 0.01), CYP11A (P < 0.05), HSD3B1 (P < 0.01), CYP17 (P < 0.05), and LHR (P < 0.05). This provides the first evidence of increased thecal androgenic capacity in the absence of a PCOS phenotype, suggesting a thecal defect induced during fetal life.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgens / biosynthesis*
  • Androstenedione / biosynthesis
  • Animals
  • Cholesterol Side-Chain Cleavage Enzyme / genetics
  • Disease Models, Animal
  • Female
  • Gene Expression / drug effects
  • Humans
  • Hydroxysteroid Dehydrogenases / genetics
  • Hypothalamo-Hypophyseal System / drug effects
  • Hypothalamo-Hypophyseal System / metabolism
  • In Vitro Techniques
  • Ovary / drug effects
  • Ovary / metabolism
  • Ovary / pathology
  • Phosphoproteins / genetics
  • Polycystic Ovary Syndrome / etiology*
  • Polycystic Ovary Syndrome / genetics
  • Polycystic Ovary Syndrome / metabolism*
  • Polycystic Ovary Syndrome / pathology
  • Pregnancy
  • Prenatal Exposure Delayed Effects / etiology
  • Prenatal Exposure Delayed Effects / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, LH / genetics
  • Sheep, Domestic
  • Steroid 17-alpha-Hydroxylase / genetics
  • Testosterone Propionate / administration & dosage
  • Theca Cells / metabolism*
  • Virilism / etiology
  • Virilism / genetics
  • Virilism / metabolism

Substances

  • Androgens
  • Phosphoproteins
  • RNA, Messenger
  • Receptors, LH
  • steroidogenic acute regulatory protein
  • Androstenedione
  • Hydroxysteroid Dehydrogenases
  • Steroid 17-alpha-Hydroxylase
  • Cholesterol Side-Chain Cleavage Enzyme
  • Testosterone Propionate