Mechanisms regulating angiogenesis underlie seasonal control of pituitary function

Seasonal changes in mammalian physiology, such as those affecting reproduction, hibernation and metabolism, are controlled by pituitary hormones released in response to annual environmental changes. In temperate zones, the primary environmental cue driving seasonal reproductive cycles is the change in daylength (photoperiod), encoded by the pattern of melatonin secretion from the pineal gland. However, although reproduction relies on hypothalamic gonadotrophin-releasing hormone (GnRH) output, and most cells producing reproductive hormones are in the pars distalis (PD) of the pituitary, melatonin receptors are localized in the pars tuberalis (PT), a physically and functionally separate part of the gland. How melatonin in the PT controls the PD is not understood. Here we show that melatonin time-dependently acts on its receptors in the PT to alter splicing of vascular endothelial growth factor (VEGF). Outside the breeding season, angiogenic VEGF-A stimulates vessel growth in the infundibulum, aiding vascular communication between the PT, PD and brain. This also acts on VEGFR2 expressed in PD prolactin-producing cells known to impair gonadotrophin secretion. In contrast, in the breeding season, melatonin releases anti-angiogenic VEGF-Axxxb from the PT, inhibiting infundibular angiogenesis and diminishing lactotroph VEGFR2 expression, lifting reproductive axis repression in response to shorter day lengths. The time-dependent, melatonin-induced differential expression of VEGF-A isoforms culminates in alterations in gonadotroph function opposite to those of lactotrophs, with up-regulation and down-regulation of gonadotropin gene expression during the breeding and non-breeding season, respectively. These results provide a novel mechanism by which melatonin can control pituitary function in a seasonal manner

Mechanisms regulating angiogenesis underlie seasonal control of pituitary function

Seasonal changes in mammalian physiology, such as those affecting reproduction, hibernation and metabolism, are controlled by pituitary hormones released in response to annual environmental changes. In temperate zones, the primary environmental cue driving seasonal reproductive cycles is the change in daylength (photoperiod), encoded by the pattern of melatonin secretion from the pineal gland. However, although reproduction relies on hypothalamic gonadotrophin-releasing hormone (GnRH) output, and most cells producing reproductive hormones are in the pars distalis (PD) of the pituitary, melatonin receptors are localized in the pars tuberalis (PT), a physically and functionally separate part of the gland. How melatonin in the PT controls the PD is not understood. Here we show that melatonin time-dependently acts on its receptors in the PT to alter splicing of vascular endothelial growth factor (VEGF). Outside the breeding season, angiogenic VEGF-A stimulates vessel growth in the infundibulum, aiding vascular communication between the PT, PD and brain. This also acts on VEGFR2 expressed in PD prolactin-producing cells known to impair gonadotrophin secretion. In contrast, in the breeding season, melatonin releases anti-angiogenic VEGF-Axxxb from the PT, inhibiting infundibular angiogenesis and diminishing lactotroph VEGFR2 expression, lifting reproductive axis repression in response to shorter day lengths. The time-dependent, melatonin-induced differential expression of VEGF-A isoforms culminates in alterations in gonadotroph function opposite to those of lactotrophs, with up-regulation and down-regulation of gonadotropin gene expression during the breeding and non-breeding season, respectively. These results provide a novel mechanism by which melatonin can control pituitary function in a seasonal manner

Pubertad en hembras bovinas, determinación de la edad a la pubertad mediante el dosaje de progesterona por radioinmunoensayo en cuatro grupos genéticos bovinos: su correlación con peso y alzada

Facultad de Ciencias Veterinaria

Intrapituitary mechanisms underlying the control of fertility:key players in seasonal breeding

AbstractRecent studies have shown that, in conjunction with dynamic changes in the secretion of GnRH from the hypothalamus, paracrine interactions within the pituitary gland play an important role in the regulation of fertility during the annual reproductive cycle. Morphological studies have provided evidence for close associations between gonadotropes and lactotropes and gap junction coupling between these cells in a variety of species. The physiological significance of this cellular interaction was supported by subsequent studies revealing the expression of prolactin receptors in both the pars distalis and pars tuberalis regions of the pituitary. This cellular interaction is critical for adequate gonadotropin output because, in the presence of dopamine, prolactin can negatively regulate the LH response to GnRH. Receptor signaling studies showed that signal convergence at the level of protein kinase C and phospholipase C within the gonadotrope underlies the resulting inhibition of LH secretion. Although this is a conserved mechanism present in all species studied so far, in seasonal breeders such as the sheep and the horse, this mechanism is regulated by photoperiod, as it is only apparent during the long days of spring and summer. At this time of year, the nonbreeding season of the sheep coincides with the breeding season of the horse, indicating that this inhibitory system plays different roles in short- and long-day breeders. Although in the sheep, it contributes to the complete suppression of the reproductive axis, in the horse, it is likely to participate in the fine-tuning of gonadotropin output by preventing gonadotrope desensitization. The photoperiodic regulation of this inhibitory mechanism appears to rely on alterations in the folliculostellate cell population. Indeed, electron microscopic studies have recently shown increased folliculostellate cell area together with upregulation of their adherens junctions during the spring and summer. The association between gonadotropes and lactotropes could also underlie an interaction between the gonadotropic and prolactin axes in the opposite direction. In support of this alternative, a series of studies have demonstrated that GnRH stimulates prolactin secretion in sheep through a mechanism that does not involve the mediatory actions of LH or FSH and that this stimulatory effect of GnRH on the prolactin axis is seasonally regulated. Collectively, these findings highlight the importance of intercellular communications within the pituitary in the control of gonadotropin and prolactin secretion during the annual reproductive cycle in seasonal breeders

Pubertad en hembras bovinas, determinación de la edad a la pubertad mediante el dosaje de progesterona por radioinmunoensayo en cuatro grupos genéticos bovinos: su correlación con peso y alzada

Facultad de Ciencias Veterinaria