Prenatal Testosterone Exposure Disrupts Insulin Secretion And Promotes Insulin Resistance.

Area of Science:

• Reproductive Endocrinology
• Metabolic Physiology
• Developmental Origins of Health and Disease

Background:

• Prenatal exposure to androgens, like testosterone, is linked to polycystic ovary syndrome (PCOS) and postnatal metabolic disturbances.
• Previous studies show reduced insulin sensitivity (IS) in female sheep exposed to testosterone in utero, persisting into reproductive life.
• The impact of postnatal testosterone on IS in females with prenatal androgen exposure remains unclear.

Purpose of the Study:

• To investigate the effects of acute postnatal testosterone administration on insulin sensitivity and secretion in adult female sheep with or without prenatal testosterone exposure.
• To determine if abnormal postnatal androgen levels exacerbate insulin resistance originating from prenatal androgen excess.

Main Methods:

• An intravenous glucose tolerance test (IVGTT) was used to assess insulin sensitivity and secretion.
• Ovariectomized female sheep, prenatally exposed to testosterone (T-females) or controls (C-females), received an acute testosterone dose (40 mg) at 40 weeks of age.
• Insulin secretion and insulin sensitivity (ISI-Composite) were measured before and after testosterone administration.

Main Results:

• Insulin secretion, indicated by the incremental area under the curve, was higher in control females, with or without acute testosterone treatment.
• Insulin sensitivity (ISI-Composite) decreased following acute testosterone treatment, but only in the T-females group.
• Prenatal testosterone exposure disrupted pancreatic insulin secretion in response to glucose.

Conclusions:

• Prenatal androgen exposure negatively impacts pancreatic insulin secretion.
• Subsequent hyperandrogenemia in adulthood may further compromise insulin sensitivity in females with a history of prenatal androgen excess.
• These findings suggest a dual role for androgen exposure in the development of metabolic dysfunction, relevant to conditions like PCOS.