Control of β-endorphin secretion into the peripheral blood of the Soay ram.
The major aim of the experiments described in this thesis was to investigate the putative mechanisms that are involved in the control of B- endorphin (B-END) secretion into the peripheral blood of the Soay ram. In addition, the effect of 8-END and adrenocorticotrophin (ACTE1) on cortisol secretion was investigated.A series of experiments was carried out to assess the influence of season, photoperiod, melatonin implantation, pinealectomy, castration and testosterone replacement on B-END secretion. There were significant changes in the plasma concentrations of B-END related to season and photoperiod in rams kept outside and inside, respectively. In outdoor rams B-END levels were highest in autumn and lowest in winter; in indoor rams the levels were highest during short days and lowest during long days. Melatonin implantation in outdoor rams from May to August caused a significant increase in B-END secretion, indicating a melatonin-induced short-day effect inspite of the prevailing long days. Pinealectomy disrupted the seasonal cycle in B-END secretion. Castration and testostrone replacement in indoor rams did not influence B-END secretion. These results indicate that B-END secretion is strongly influenced by season and photoperiod (via melatonin from the pineal gland) and that testosterone plays no role in B-END secretion.In another series of experiments, the roles of arginine vasopressin (AVP), corticotrophin releasing factor (CRF), the synthetic glucocorticoid, dexamethasone (DEX) and the synthetic glucocorticoid antagonist, RU 486, in the control of the seasonal cycle in B-END secretion were investigated in spring, summer, autumn and winter. AVP and CRF given alone or in combination significantly stimulated 8-END secretion at all seasons and acted synergistically when given together. The responses were greater in summer and autumn than in winter and spring. DEX suppressed 8-END secretion at all seasons and the responses were also greater in summer and autumn. DEX also blocked the AVP-induced increase in 8-END secretion, indicating an action of DEX at the pituitary gland. RU 486 given in summer and winter significantly stimulated 8-END secretion only in winter, indicating a seasonal variation in the negative feedback action of endogenous glucocorticoids. In addition, ACTH, but not 8-END, significantly stimulated cortisol secretion at all seasons, with the greatest response in spring. These studies indicate that AVP, CRF and glucocorticoids are involved in the control of the seasonal cycle in 8-END secretion; and that ACTH rather than 8-END constitutes the " drive " to cortisol secretion.The roles of dopamine (DA) and endogenous opioid peptides (EOP) in the control of 8-END secretion were also investigated. The mixed DA antagonist, pimozide, significantly increased 8-END secretion under long and short days; with a greater effect under long days.The D2 agonist, bromocriptine, and the D2 antagonist, sulpiride, significantly decreased and increased, respectively, 8-END secretion both under long and short days. The opioid antagonist, naloxone, had no effect on 8-END secretion. These studies indicate that DA exerts an inhibitory control over 8-END secretion while the EOP play no role in 8-END secretion.Based on the current results and a survey of the relevant literature, a model is proposed in which AVP, CRF, glucocorticoids on one hand, and DA on the other hand, are involved in the control of the secretory activity of corticotrophs and melanotrophs in the pituitary gland. These central mechanisms are influenced by changes in photoperiod and other environmental factors to dictate the seasonal cycle in 6-END secretion in the Soay ram, which is low in winter and high in autumn. To fully assess the importance of AVP, CRF and DA in the seasonal control of 6-END secretion, it will be necessary to directly measure the concentration of these hormones in the hypophysial portal circulation of Soay rams at different seasons.