Prenatal Androgenization of Ewes as a Model of Hirsutism in Polycystic Ovary Syndrome

Endocrinology. 2018 Dec 1;159(12):4056-4064. doi: 10.1210/en.2018-00781.

Abstract

The main clinical feature associated with hyperandrogenism in polycystic ovary syndrome (PCOS) in humans is hirsutism, where hair increases its length, pigmentation, and particularly its diameter. Currently, it is not known whether PCOS animal models also exhibit changes in the hair. Therefore, the aim of this study was to explore the wool characteristics in sheep prenatally androgenized (PA) with testosterone propionate. After 4 and 13 months of life, wool was collected from the top of the shoulder of both females and males (both androgenized and controls). The offspring sheep were followed for up to 19 months of life to evaluate testosterone and androstenedione serum levels by ultra-high-performance liquid chromatography-tandem mass spectrometry, determine insulin and glucose response to intravenous glucose tolerance test, and address estrus cyclicity during the second breeding season. PA male animals showed a reduction in wool fiber diameter at 4 months of age compared with controls (P = 0.02) but not at 13 months, whereas PA females showed increased hair diameter at 13 months (P = 0.002), with no difference at 4 months. No substantial changes in other hair parameters (length, color, and medullation) were identified. In addition, increased levels of serum testosterone were observed in PA female sheep compared with controls at 12 months (P = 0.03). Our results indicate for the first time, to our knowledge, that changes in wool fiber diameter observed in PA ewes replicate, at the translational level, the increase in hair diameter in hirsute women with PCOS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgens*
  • Animals
  • Disease Models, Animal*
  • Female
  • Glucose Tolerance Test
  • Hirsutism* / blood
  • Hirsutism* / chemically induced
  • Hirsutism* / complications
  • Hirsutism* / pathology
  • Hyperandrogenism / blood
  • Hyperandrogenism / chemically induced
  • Hyperandrogenism / pathology
  • Male
  • Polycystic Ovary Syndrome* / blood
  • Polycystic Ovary Syndrome* / complications
  • Polycystic Ovary Syndrome* / pathology
  • Pregnancy
  • Prenatal Exposure Delayed Effects / blood
  • Prenatal Exposure Delayed Effects / chemically induced*
  • Prenatal Exposure Delayed Effects / pathology
  • Sheep*
  • Testosterone Propionate
  • Virilism / blood
  • Virilism / chemically induced*
  • Virilism / pathology

Substances

  • Androgens
  • Testosterone Propionate