Prenatal androgens time neuroendocrine sexual maturation

Area of Science:

• Reproductive Endocrinology
• Neuroendocrinology
• Developmental Biology

Background:

• Significant sex differences exist in the timing of neuroendocrine sexual maturation in sheep.
• Male lambs typically show reduced sensitivity to gonadal steroid feedback earlier than females.
• The role of prenatal hormonal environment in programming these sex differences is not fully understood.

Purpose of the Study:

• To determine if in utero exposure to gonadal steroids influences postnatal control of gonadotropin secretion in lambs.
• To test the hypothesis that prenatal androgens advance the pubertal decrease in steroid feedback sensitivity.
• To investigate the impact of prenatal androgenization on the timing of pulsatile gonadotropin secretion.

Main Methods:

• Pregnant ewes were injected with testosterone cypionate during gestation to androgenize fetuses.
• Lambs (androgenized females/males, control females/males) were gonadectomized and implanted with estradiol for constant feedback.
• Luteinizing hormone (LH) secretion was monitored via biweekly blood samples and frequent sampling for pulse frequency analysis.

Main Results:

• Androgenized male lambs exhibited an earlier decrease in steroid feedback sensitivity (5.4 weeks) compared to controls (10.1 weeks).
• Control female lambs remained hypersensitive to feedback until 27.2 weeks, while androgenized females showed intermediate responses.
• Prenatal androgen exposure in females led to earlier LH secretion and increased LH pulse frequency, correlating with genital masculinization.

Conclusions:

• Prenatal androgens can significantly masculinize gonadotropin secretion patterns in sheep.
• The timing of reproductive neuroendocrine maturation after birth is programmed by in utero androgen exposure.
• This study provides evidence for hormonal imprinting during fetal development influencing adult reproductive physiology.