The recovery of ovine pars tuberalis cells from melatonin-induced sensitization is a slow, protein synthesis-dependent phenomenon

Abstract

The pars tuberalis (PT) of the anterior pituitary is characterized by the presence of a high concentration of melatonin receptors, and acute exposure of cells from this tissue to melatonin inhibits the accumulation of cyclic AMP (cAMP) stimulated by forskolin. Conversely, exposure of ovine PT (oPT) cells to melatonin for periods of up to 16 h causes a progressive increase in subsequent basal and forskolin-stimulated production of cAMP. These observations are consistent with the possibility that the PT is involved in the mediation of melatonin-dependent phenomena in mammals. If the chronic effects of exposure to melatonin are indeed functionally significant, then one would anticipate that those responses of oPT cells known to be dependent upon levels of cAMP would also show an enhanced response to stimulation following prolonged exposure to the hormone. In the present study, the activation of cAMP-dependent protein kinase and the synthesis of secretory protein by oPT cells were found to be sensitized by prolonged exposure to physiological concentrations of melatonin. In the case of the synthesis of secretory protein this effect of melatonin was confined to those proteins whose synthesis has been shown to be sensitive to melatonin in acute experiments. These observations support the hypothesis that melatonin-induced sensitization modulates the putative biosynthetic and secretory function of the PT. The present study also examined the mechanism of sensitization of oPT cells by melatonin. The development of sensitization was not affected by simultaneous exposure of oPT cells to forskolin (1 microM) during pretreatment with melatonin. This observation suggests that melatonin-induced sensitization occurs independently of the established acute effects of the hormone on cAMP levels in oPT cells. Since no effects of melatonin upon any other signalling cascade have been observed in these cells, the most plausible explanation for this finding is that sensitization is a direct consequence of prolonged activation of melatonin receptors. Such a mechanism might be linked to the partial down-regulation of melatonin receptors known to occur in oPT cells in response to prolonged exposure to the hormone. In order to test this hypothesis further, the process of recovery from the sensitizing effects of melatonin was examined. The recovery of oPT cells from the sensitizing effects of exposure to melatonin (100 pM, 16 h) took place gradually and, even after an interval of 16 h, cells that had previously been exposed to melatonin for 16 h remained sensitized to approximately 20% of the extent seen immediately following pretreatment with melatonin for 16 h.(ABSTRACT TRUNCATED AT 400 WORDS)

Evidence for Gene Transcription of Adenohypophyseal Hormones in the Ovine Pars tuberalis

“…Recently, sensitization of PT cells in terms of basal and forskolin-stimulated cAMP production as w'ell as synthe sis of secretory proteins was reported in response to chronic incubation with physiological concentrations of melatonin in vitro [40], Although prolonged exposure of the PT to melatonin seems to be functionally significant, in light of the present study it remains to be established why no putative secretory products can be found indepen dent of the photoperiod.…”

Role of the Pituitary Gland in the Development of Photorefractoriness and Generation of Long-Term Changes in Prolactin Secretion in Rams

“…Melatonin inhibits cAMP-induced activation of protein synthesis and secretion by ovine PT cells [27,28], and there is evidence that PT cells in primary culture secrete factors that promote PRL secretion [29]. PT cells also vary their cellular response depending on the timing or duration of exposure to melatonin [30,31]. This includes the activation of the early response gene oPer1 [32]; thus the PT may have clock-like properties.…”

The effect of nutrition on the neural mechanisms potentially involved in melatonin-stimulated LH secretion in female Mediterranean goats

“…A possible explanation is that the secretion of GNRH/LH in response to the exclusion of the inhibitory tone of endogenous opioids becomes intensified by melatonin at the cellular level. Certainly, studies on the pars tuberalis cells have revealed that cAMP is dramatically elevated following simultaneous treatment with adenylate cyclase activators and melatonin (Hazlerigg et al 1994, Barrett et al 2003. Melatonin can induce a sensitised response to adenylate cyclase in ovine pars tuberalis cells, in which the receptor for melatonin is endogenously expressed (Barrett et al 2003).…”