of sperm sufficient for those to appear in the ejaculate, the physiological event that characterizes puberty (see Chapter 6).
Metabolic Hormones During the Prepubertal and Pubertal Periods
The mechanisms controlling reproduction and energy balance are intrinsically related and have evolved to confer reproductive advantages and guarantee the survival of species. The neural apparatus designed to gauge metabolic rate and energy balance has been denominated the body “metabolic sensor.” This sensor translates signals provided by circulating (peripheral) concentrations of specific hormones into neuronal signals that ultimately regulate the GnRH pulse generator and control the reproductive process. Metabolic indicator hormones may serve as signs to the hypothalamus–pituitary–gonadal axis and affect sexual development. The patterns of some of these hormones have been studied in growing beef bulls (Figure 5.6). In contrast to species in which circulating growth hormone (GH) concentrations continue to increase until after puberty, GH concentrations decrease during the pubertal period in bulls [2, 5]. Differences in the stage of body development at which each species attains puberty are likely responsible for the different GH profiles among species. Accordingly, the GH profile in bulls seems to indicate that a relatively advanced stage of body development must be attained before the gonads are efficiently producing sperm. The differences in GH secretion among species may be due to the regulatory role of steroids on GH secretion. In other species, steroids stimulate GH secretion, but GH concentrations do not differ between intact bulls and castrated steers [42]. Moreover, decreasing GH concentrations during sexual development are observed along with increasing testosterone concentrations, indicating that steroids do not have a positive feedback on GH secretion in bulls as in other species [2, 5].
Figure 5.6 Mean (± SEM) serum IGF‐I, insulin, GH, and leptin concentrations during sexual development in Angus and Angus × Charolais bulls receiving adequate nutrition.
Sources: Data from [2–5].
Circulating insulin‐like growth factor (IGF)‐I concentrations in bulls increase continuously and only reach a plateau (or decrease slightly) after sexual development is mostly completed after 12–14 months of age; increasing circulating concentrations of IGF‐binding protein 3 and decreasing concentrations of IGF‐binding protein 2 are also observed during sexual development [2–5,43–45]. The concomitant decrease in circulating GH concentrations with the increase in IGF‐I concentrations during sexual development in bulls indicates that either there are drastic changes in liver sensitivity to GH or other sources are responsible for IGF‐I production. A possible IGF‐I source might be the testes, since Leydig cells are capable of secreting this hormone in other species. Observations that intact bulls tend to have greater IGF‐I concentrations than castrated steers at 12 months of age further support the hypothesis that the testes might contribute substantially to circulating IGF‐I concentrations during the prepubertal and pubertal periods in bulls [42]. Close temporal associations observed in a series of nutrition studies strongly suggest that circulating IGF‐I might be involved in regulating the GnRH pulse generator and the magnitude and duration of the early gonadotropin rise in beef bulls [2–4, 33].
A possible effect of IGF‐I on testicular steroidogenesis in bulls has also been suggested. Leydig and Sertoli cells produce IGF‐I, indicating the existence of paracrine/autocrine mechanisms of testicular regulation involving IGF‐I [46, 47]. It is assumed that most of the IGF‐I in the testes is produced locally and that circulating IGF‐I may play a secondary role in regulating testicular development and function. However, the temporal patterns and strong associations among circulating IGF‐I concentrations, testicular size, and testosterone secretion observed in bulls receiving different nutrition argue for a primary role for this hormone [2–4, 33, 35]. The primary role of increased circulating IGF‐I during the pubertal period may be to promote the increase in testosterone concentrations by regulating Leydig cell multiplication, differentiation, and maturation. Since testosterone upregulates IGF‐I production and IGF‐I receptor expression by Leydig and Sertoli cells [48], the establishment of a positive feedback loop between IGF‐I secretion and testosterone production may be important for sexual development.
Circulating leptin and insulin concentrations also increase during the pubertal period in bulls. However, developmental and nutritional differences in LH pulse frequency are not related to differences in leptin or insulin concentrations in beef or dairy bulls [2, 3, 35]. Other studies have also demonstrated that leptin does not stimulate in vitro GnRH secretion from hypothalamic explants or gonadotropin secretion from adenohypophyseal cells collected from bulls and steers maintained at an adequate 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
