Regional differences in the distribution of gonadotropin-releasing hormone cells between rapidly growing and growth-restricted prepubertal female sheep.

Growth retardation induced by dietary restriction in the lamb results in a low GnRH pulse frequency, and thus, puberty is delayed. In our experimental model, in which ovariectomized lambs are maintained at weaning weight (approximately 20 kg BW), hypothalamic GnRH is present and releasable, suggesting that central mechanisms limit the release of GnRH during chronic growth restriction. Our study compared the number and distribution of GnRH-containing neurons in growth-restricted (n = 5) and rapidly growing (n = 5) ovariectomized prepubertal female lambs at 24 weeks of age (normal age of puberty is about 30 weeks). Immunoreactive cells were labeled using LR-1 antiserum (R. Benoit) and an avidin-biotin-immunoperoxidase procedure. GnRH neurons were localized in 60-micron coronal sections from the level of the diagonal band of Broca to the mammillary bodies. The estimated total number of GnRH neurons in the growth-restricted and rapidly growing lambs was similar (3364.8 +/- 513.8 vs. 3151.2 +/- 279.8, respectively). In addition, the percent distributions of GnRH neurons in the diagonal band of Broca, the anterior hypothalamus, the lateral hypothalamus, and the posterior hypothalamus were not different. A trend (P = 0.07) toward a smaller percent distribution in the preoptic area was noted in growth-restricted lambs (30.6 +/- 3.6) compared to rapidly growing lambs (44.0 +/- 5.2). By contrast, the percent distribution of GnRH neurons in the medial basal hypothalamus was significantly greater in the growth-restricted lambs compared with the rapidly growing lambs (17.7 +/- 2.2 vs. 6.7 +/- 1.4, respectively; P < 0.005). It is of interest that the percent distribution of GnRH-containing neurons in the medial basal hypothalamus of the hypogonadotropic growth-restricted lamb is similar to that observed in the fetal lamb, whereas the eugonadotropic rapidly growing lamb is more similar to the adult female. In this context, decreased GnRH secretion and delayed puberty during diet-induced growth restriction may arise from alterations in the GnRH neurosecretory system.