Prenatal testosterone exposure leads to gonadal hormone-dependent hyperinsulinemia and gonadal hormone-independent glucose intolerance in adult male rat offspring

Amar S. More, Jay S. Mishra, Kathirvel Gopalakrishnan, Chellakkan S. Blesson, Gary Hankins, Kunju Sathishkumar

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Elevated testosterone levels during prenatal life lead to hyperandrogenism and insulin resistance in adult females. This study evaluated whether prenatal testosterone exposure leads to the development of insulin resistance in adult male rats in order to assess the influence of gonadal hormones on glucose homeostasis in these animals. Male offspring of pregnant rats treated with testosterone propionate or its vehicle (control) were examined. A subset of male offspring was orchiectomized at 7 wk of age and reared to adulthood. At 24 wk of age, fat weights, plasma testosterone, glucose homeostasis, pancreas morphology, and gastrocnemius insulin receptor (IR) beta levels were examined. The pups born to testosterone-treated mothers were smaller at birth and remained smaller through adult life, with levels of fat deposition relatively similar to those in controls. Testosterone exposure during prenatal life induced hyperinsulinemia paralleled by an increased HOMA-IR index in a fasting state and glucose intolerance and exaggerated insulin responses following a glucose tolerance test. Prenatal androgenexposed males had more circulating testosterone during adult life. Gonadectomy prevented hyperandrogenism, reversed hyperinsulinemia, and attenuated glucose-induced insulin responses but did not alter glucose intolerance in these rats. Prenatal androgen-exposed males had decreased pancreatic islet numbers, size, and beta-cell area along with decreased expression of IR in gastrocnemius muscles. Gonadectomy restored pancreatic islet numbers, size, and beta-cell area but did not normalize IRbeta expression. This study shows that prenatal testosterone exposure leads to a defective pancreas and skeletal muscle function in male offspring. Hyperinsulinemia during adult life is gonad-dependent, but glucose intolerance appears to be independent of postnatal testosterone levels.

Original languageEnglish (US)
Article number5
JournalBiology of Reproduction
Volume94
Issue number1
DOIs
StatePublished - Jan 1 2016

Fingerprint

Gonadal Hormones
Glucose Intolerance
Hyperinsulinism
Testosterone
Insulin Receptor
Hyperandrogenism
Islets of Langerhans
Cell Size
Glucose
Insulin Resistance
Pancreas
Skeletal Muscle
Homeostasis
Fats
Insulin
Testosterone Propionate
Gonads
Glucose Tolerance Test
Androgens
Fasting

Keywords

  • Developmental programing
  • Glucose intolerance
  • Gonadectomy
  • Hyperinsulinemia
  • Insulin resistance
  • Pancreas

ASJC Scopus subject areas

  • Cell Biology

Cite this

Prenatal testosterone exposure leads to gonadal hormone-dependent hyperinsulinemia and gonadal hormone-independent glucose intolerance in adult male rat offspring. / More, Amar S.; Mishra, Jay S.; Gopalakrishnan, Kathirvel; Blesson, Chellakkan S.; Hankins, Gary; Sathishkumar, Kunju.

In: Biology of Reproduction, Vol. 94, No. 1, 5, 01.01.2016.

Research output: Contribution to journalArticle

More, Amar S. ; Mishra, Jay S. ; Gopalakrishnan, Kathirvel ; Blesson, Chellakkan S. ; Hankins, Gary ; Sathishkumar, Kunju. / Prenatal testosterone exposure leads to gonadal hormone-dependent hyperinsulinemia and gonadal hormone-independent glucose intolerance in adult male rat offspring. In: Biology of Reproduction. 2016 ; Vol. 94, No. 1.
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