Prenatally testosterone (T)-treated female sheep exhibit ovarian and endocrinological features that resemble those of women with polycystic ovarian syndrome (PCOS), which include luteinizing hormone excess, polyfollicular ovaries, functional hyperandrogenism, and anovulation. In this study, we determined the developmental impact of prenatal T treatment on insulin sensitivity indexes (ISI), a variable that is affected in a majority of PCOS women. Pregnant ewes were treated with 60 mg testosterone propionate intramuscularly in cottonseed oil two times a week or vehicle [control (C)] from days 30 to 90 of gestation. T-females weighed less than C-females or males (P < 0.05) at birth and at 5 wk of age. T-females had an increased anogenital ratio. An intravenous glucose tolerance test followed by an insulin tolerance test conducted after an overnight fast at 5, 20, and 30 wk of age (n = 7-8/group) revealed that ISI were higher at 5 than 30 wk of age in C-females, reflective of a developing insulin resistance associated with puberty. T-females had higher basal insulin levels, higher fasting insulin-to-glucose ratio, and higher incremental area under the insulin curve to the glucose challenge. The ISI of T-females was similar to that of males. No differences in ISI were evident between groups at 20 and 30 wk of age. Mean basal plasma glucose concentrations and glucose disappearance and uptake did not differ between groups at any age. Our findings suggest that prenatal T treatment leads to offspring with reduced birth weight and impaired insulin sensitivity in early postnatal life.

Although activation of the hypothalamic GnRH pulse generator is known to initiate the onset of puberty in immature animals, the metabolic cues by which information about the stage of body growth and development are translated into central nervous activity remain obscure. In the present study, the function of L-arginine (ARG) or L-ornithine (ORN) as promoters of pulsatile LH secretion was investigated in 2-mo-old prepubertal ewes. Suffolk ewe lambs (n = 17) fitted with intrajugular catheters were divided into three groups. Saline (200 mL) was infused for 1 h into all lambs. In Group 1, saline infusion was continued for another hour. In Group 2, 200 mL of an ARG solution (350 mM, pH 7.4) was infused for 1 h, and in Group 3, ORN was infused (200 mL, 350 mM, pH 7.4) for 1 h. Blood samples were collected at 15-min intervals from 60 min before until 285 min after the end of infusions. The Pulsar program was used to identify significant LH episodes during 285 min after infusions. Mean LH concentrations during the 285-min period after infusion were greater (P < .05) in Group 2 than in Groups 1 and 3. The mean LH pulse frequencies and amplitudes did not differ among the groups. However, in lambs infused with ARG, 13 of their 17 LH pulses had amplitudes > 1 ng/mL, whereas in control ewes only 5 of 20 pulses had amplitudes > 1 ng/mL. All of the ARG-infused ewes had two or more LH pulses with amplitudes > 1 ng/mL; only 1 of 6 control lambs had two pulses. Results indicate that ARG stimulates LH secretion in prepubertal ewes.

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