Elevated androstenedione in young adult but not early adolescent prenatally androgenized female rats

PLoS One. 2018 May 3;13(5):e0196862. doi: 10.1371/journal.pone.0196862. eCollection 2018.

Abstract

Background: Elevated testosterone (T) is routinely reported as a marker of hyperandrogenemia in rodent models for polycystic ovary syndrome (PCOS). In women with PCOS, elevated serum androstenedione (A4) is associated with more severe phenotypes, including a positive correlation with serum T, DHEAS, free androgen index (FAI), LH, and LH/FSH ratio. Furthermore, A4, along with calculated free T and FAI, was identified as one of the best predictors of PCOS in adult women of all ages (18 to > 50 y).

Objective: The objective of this study was to investigate serum A4 levels in early adolescent and young adult prenatally androgenized (PNA) female rats, a model for PCOS.

Methods: Pregnant rats were injected with 5 mg T daily during gestational days 16-19 (PNA rats, experimental group) or an equal volume of vehicle (control group). Female offspring of both groups had tail vein blood drawn for serum analysis at 8 and 16 weeks of age. ELISAs were used to quantify serum A4 and T levels.

Results: Serum A4 and T were elevated in 16-week-old PNA rats compared to controls. There was no significant difference in either hormone at 8 weeks of age.

Conclusions: The PNA rats demonstrated elevated serum A4 and T in young adulthood, as has been observed in women with PCOS, further validating this as a model for PCOS and underscoring the importance of serum A4 elevation as a parameter inherent to PCOS and a rodent model for the disorder. Significant A4 elevation develops between early adolescence and early adulthood in this PNA rat model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / blood*
  • Androstenedione / blood*
  • Animals
  • Animals, Newborn
  • Biomarkers / blood
  • Disease Models, Animal
  • Female
  • Follicle Stimulating Hormone / blood
  • Hyperandrogenism / blood*
  • Hyperandrogenism / chemically induced
  • Hyperandrogenism / pathology
  • Luteinizing Hormone / blood
  • Ovary / drug effects
  • Ovary / metabolism
  • Ovary / pathology
  • Polycystic Ovary Syndrome / blood*
  • Polycystic Ovary Syndrome / chemically induced
  • Polycystic Ovary Syndrome / pathology
  • Pregnancy
  • Prenatal Exposure Delayed Effects / blood*
  • Prenatal Exposure Delayed Effects / chemically induced
  • Prenatal Exposure Delayed Effects / pathology
  • Rats
  • Rats, Sprague-Dawley
  • Sexual Maturation
  • Testosterone / administration & dosage*
  • Testosterone / blood

Substances

  • Biomarkers
  • Testosterone
  • Androstenedione
  • Luteinizing Hormone
  • Follicle Stimulating Hormone

Grants and funding

This work was supported by a Lake Erie College of Osteopathic Medicine and Lake Erie Consortium for Osteopathic Medical Training grant to D.L.S. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.