Hypophysial angiogenesis decodes annual time and underlies physiological adaptation to seasonal changes in the environment.

Adaptation to annual changes in the environment is controlled by hypophysial hormones. In temperate zones, photoperiod is the primary external cue that regulates annual biological cycles and is translated by the pattern of melatonin secretion acting primarily in the hypophysial pars tuberalis. Angiogenic mechanisms within this tissue contribute to decode the melatonin signal through alternative splicing of the vascular endothelial growth factor A (VEGF-A) gene in both the pars tuberalis and the capillary loops of the infundibulum.

Physiological Role of Vascular Endothelial Growth Factors as Homeostatic Regulators.

The vascular endothelial growth factor (VEGF) family of proteins are key regulators of physiological systems. Originally linked with endothelial function, they have since become understood to be principal regulators of multiple tissues, both through their actions on vascular cells, but also through direct actions on other tissue types, including epithelial cells, neurons, and the immune system. The complexity of the five members of the gene family in terms of their different splice isoforms, differential translation, and specific localizations have enabled tissues to use these potent signaling molecules to control how they function to maintain their environment.

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 day length (i.e.

Cells co-expressing luteinising hormone and thyroid-stimulating hormone are present in the ovine pituitary pars distalis but not the pars tuberalis: implications for the control of endogenous circannual rhythms of prolactin.

Background/aims: A mammalian circannual pacemaker responsible for regulating the seasonal pattern of prolactin has been recently described in sheep. This pacemaker resides within the pars tuberalis, an area of the pituitary gland that densely expresses melatonin receptors. However, the chemical identity of the cell type which acts as the pacemaker remains elusive.

Photoperiodic modulation of the suppressive actions of prolactin and dopamine on the pituitary gonadotropin responses to gonadotropin-releasing hormone in sheep.

In a variety of species, the LH-secretory response to gonadotropin-releasing hormone (GnRH) is completely suppressed by the combined actions of prolactin (PRL) and dopamine (DA). In sheep, this effect is only observed under long days (nonbreeding season [NBS]). To investigate the level at which these mechanisms operate, we assessed the effects of PRL and bromocriptine (Br), a DA agonist, on the gonadotropin-secretory and mRNA responses to GnRH in pituitary cell cultures throughout the ovine annual reproductive cycle.

Characterization of the effects of prolactin in gonadotroph target cells.

Hyperprolactinemia is a major cause of infertility, brought about by inhibition of gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus and impairment of luteinizing hormone (LH) output from the pituitary gland. However, whereas the actions of prolactin (PRL) within the brain have been investigated extensively, its specific effects at the level of pituitary gonadotroph target cells remain unclear. Here, we provide evidence that the actions of PRL within the gonadotroph are more complex than originally envisaged.

Gonadotrophin subunit and GnRH receptor gene expression in the pars distalis of the equine pituitary.

In the horse, pronounced changes in fertility occur annually in response to photoperiod. However, the mechanisms regulating gonadotrophin synthesis and release in this species remain unclear. Here, we investigated the expression of gonadotrophin subunits and GnRH receptor (GnRH-R) mRNA in the pituitary glands of Thoroughbred horses during the breeding (BS) and non-breeding (NBS) season.

Direct effects of prolactin and dopamine on the gonadotroph response to GnRH.

The intrapituitary mechanisms underlying the inhibitory actions of hyperprolactinaemia on the reproductive axis remain unclear. Previous work on primary pituitary cultures revealed combined suppressive effects of prolactin (PRL) and dopamine on the gonadotrophin response to GnRH. However, whether these effects occur directly at the level of the gonadotroph and are accompanied by changes in gene expression is still unresolved.

Gonadotropin-releasing hormone stimulates prolactin release from lactotrophs in photoperiodic species through a gonadotropin-independent mechanism.

Previous studies have provided evidence for a paracrine interaction between pituitary gonadotrophs and lactotrophs. Here, we show that GnRH is able to stimulate prolactin (PRL) release in ovine primary pituitary cultures. This effect was observed during the breeding season (BS), but not during the nonbreeding season (NBS), and was abolished by the application of bromocriptine, a specific dopamine agonist.

Endogenous circannual cycles of ovarian activity and changes in prolactin and melatonin secretion in wild and domestic female sheep maintained under a long-day photoperiod.

The present study examines the ovulatory activity of wild and domesticated ewes subjected to either a constant photoperiod of long days (16L:8D) or natural changes in daily photoperiod for 16 mo. The aim was to determine whether an endogenous reproductive rhythm controls seasonal reproductive activity in these sheep, and how the photoperiod might affect this. The effects of long-day photoperiods on long-term changes in prolactin and melatonin secretion were also evaluated.

Prolactin-induced activation of STAT5 within the hypothalamic arcuate nucleus.

Prolactin signalling within hypothalamic areas associated with the control of fertility was examined in male and lactating female rats. Following exogenous prolactin treatment, phosphorylation of STAT5 (signal transducer and activator of transcription) within the arcuate nucleus was measured using a highly sensitive immunoblotting strategy. A significant increase in phosphorylated STAT5 was detected in the arcuate nucleus of female rats compared with same-sex controls.

Effects of prolactin on hypothalamic supraoptic neurones: evidence for modulation of STAT5 expression and electrical activity.

Objectives: The study investigated the role of prolactin (PRL) in modulating STAT5 and electrical activity of magnocellular neurones in the supraoptic (SO) nucleus of male rats.

Methods: Evidence of expression of STAT5 in the SO nucleus was investigated by immunocytochemical methods. Effect of blocking prolactin receptors on STAT 5 expression was investigated by Western blotting following transfection of SO neurones with a dominant negative mutant form of the PRL receptor.

Effects of prolactin on the luteinizing hormone response to gonadotropin- releasing hormone in primary pituitary cell cultures during the ovine annual reproductive cycle.

In the sheep pituitary, the localization of prolactin (PRL) receptors in gonadotrophs and the existence of gonadotroph-lactotroph associations have provided morphological evidence for possible direct effects of PRL on gonadotropin secretion. Here, we investigated whether PRL can readily modify the LH response to GnRH throughout the ovine annual reproductive cycle. Cell populations were obtained from sheep pituitaries during the breeding season (BS) and the nonbreeding season (NBS), plated to monolayer cultures for 7 days, and assigned to receive one of the following treatments: 1) nil (control), 2) acute (90- min) bromocriptine (ABr), 3) chronic (7-day) bromocriptine (CBr), 4) ABr and PRL, 5) CBr and PRL, 6) PRL alone, or 7) thyrotropin-releasing hormone.

Developmental changes in the hormonal identity of gonadotroph cells in the rhesus monkey pituitary gland.

To help elucidate the regulatory mechanism responsible for divergent gonadotrophin secretion during sexual maturation, we examined the gonadotroph population and hormonal identity of gonadotroph subtypes in pituitary glands of juvenile (age, 1.7 +/- 0.2 yr) and adult (age, 12.