level of nutrition [49]. These results indicate that the role of these hormones in regulating GnRH secretion, if any, might be purely permissive in bulls.
GnRH‐Independent Testicular Development
The rapid testicular growth observed after six months of age in bulls occurs when circulating gonadotropin concentrations are decreasing, which points to the existence of important GnRH‐independent mechanisms regulating testicular development. The period of accelerated testicular growth coincides with increasing circulating IGF‐I and leptin concentrations, and strong associations between these hormones and testicular size have been observed in growing beef and dairy bulls [2, 5, 6, 33], indicating that metabolic hormones may be involved in regulating GnRH‐independent testicular development. Since there was no association between circulating metabolic hormones and gonadotropin concentrations in these studies, the possible effects of metabolic hormones on testicular growth are likely direct and independent of the hypothalamus and pituitary. Accelerated testicular growth in bulls involves increases in seminiferous tubule diameter and length, volume of testicular parenchyma occupied by seminiferous tubules, and total number of germinal cells [15, 36]. Although IGF‐I and leptin concentrations are associated with testicular size, there are no associations between these hormones and seminiferous tubule diameter and area, seminiferous epithelium area, or volume occupied by seminiferous tubule (L.F.C. Brito, unpublished results). These observations suggest that increased circulating IGF‐I and leptin concentrations are associated with increased length of the seminiferous tubules and likely with overall increases in the total number of testicular cells. Considering the cellular events in the testis during the pubertal period, the temporal patterns of metabolic hormone concentrations indicate that circulating IGF‐I and leptin could be involved in regulating Leydig cell multiplication and maturation, Sertoli cell maturation, and germ cell multiplication during the period of accelerated GnRH‐independent testicular growth in bulls.
Testicular concentrations of LH and FSH receptors in beef bulls decrease around five to six months of age, but increase thereafter until at least approximately 13 months of age, which might increase the sensitivity of Leydig and Sertoli cells to the low concentrations of gonadotropins during the rapid testicular growth phase [37]. Other mechanisms that might be associated with GnRH‐independent testicular growth include changes in testicular concentrations and bioavailability of growth factors such as transforming growth factor (TGF)‐α and TGF‐β1, TGF‐β2, and TGF‐β3 and interleukin (IL)‐1α, IL‐1β, and IL‐6 [50, 51]. In addition, experiments evaluating the effect of nutrition on sexual development have demonstrated that the impact of gonadotropins on target tissues during the prepubertal period has long‐term effects on testicular development in bulls. Bulls with either greater LH pulse frequency or more sustained increase in LH pulse frequency during the early gonadotropin rise had a more prolonged period of increased testicular growth and greater testicular size at 15–16 months of age, even when no differences in metabolic hormones or testosterone concentrations were observed after six months of age. These results indicate that the putative effects of circulating metabolic hormones, gonadotropins, local growth factors, and other unknown factors during the period of rapid testicular growth might be dependent on previous LH exposure during the prepubertal period. The LH secretion pattern during the early gonadotropin rise seems to “prime” testicular development and dictates maximum testicular size in bulls [2–4, 33].
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