Neonatal exposure to single doses of estradiol or testosterone programs ovarian follicular development–modified hypothalamic neurotransmitters and causes polycystic ovary during adulthood in the rat

Objective To investigate the hormones participating in early follicular development and hypothalamic neurotransmitters in rats during adulthood. Design Experimental basic study. Setting University animal laboratory. Animal(s) Twenty-three neonatal rats injected with single subcutaneous injection of estradiol valerate (EV), testosterone propionate (TP), or dihydrotestosterone (DHT) and killed by decapitation at 60 days of age. Intervention(s) Measurements of neurotransmitter in ventromedial hypothalamus–arcuate nucleus (VMH-AN) and ovarian morphometry in the adult rat. Main Outcome Measure(s) Noradrenaline (NA), dopamine (DA), serotonin (5-HT), glutamic acid (Glu), and gamma-aminobutyric acid (GABA) content by high performance liquid chromatography medial basal hypothalamus and ovarian morphology. Result(s) EV exposure increased 5-HT, DA, NA, and Glu and decreased GABA levels in the VMH-AN. Exposure to TP increased Glu and decreased 5-HT in the VMH-AN. Neonatal EV and TP decreased the number of primordial follicles but EV increased the atresia of antral follicles and TP decreased it. Neonatal exposure to DHT did not cause morphologic changes in the adult ovary. Conclusion(s) Neonatal exposure to EV activated the reproductive hypothalamus and permanently modified ovarian follicular development. TP exposure had some similar effects as EV at the hypothalamus, and it modified ovarian development mimicking the effects of EV. This last effect could be through TP conversion to estradiol because DHT, a nonaromatizable androgen, did not modify follicular development.