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Title: The regulation of gonadotrophin secretion following divergent selection for pituitary responsiveness to GnRH
Author: Evans, Neil Price
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1991
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Divergent selection based on the LH response to a 5μg dose of GnRH, has created two lines of sheep which differ in their ability to release gonadotrophins in response to a GnRH challenge in both male and female lambs. Significant correlated between line differences have also been reported in female reproductive performance. The aim of this project was to investigate the regulation of gonadotrophin secretion in animals from the two lines, and to elucidate the primary site of the selected difference/s. Physiological studies of adult ewes and prepubertal ram lambs demonstrated that despite similar peripheral steroid concentrations, endogenous and exogenously stimulated gonadotrophin secretion differed significantly between the two lines. Mean LH and FSH concentrations in the prepubertal male lambs were significantly higher in the High line than the Low line, due to the secretion of LH pulses of significantly greater amplitude by the High line ram lambs. Similarly, higher amplitude LH pulses were observed in the High line ewes during the follicular phase of the oestrous cycle. The age related changes in basal LH secretion in the ram lambs and the observation of significant differences in LH pulse amplitude in the adult ewes during the follicular phase of the oestrous cycle, when progesterone negative feedback is reduced, indicate that the effects of the between line difference in the regulation of endogenous LH secretion are regulated by gonadal negative feedback. However studies in prepubertal ram lambs demonstrated that the primary site of the selected difference was at the level of the hypothalamo/pituitary gland complex. Studies of the regulation of LH secretion by the hypothalamo/pituitary gland complex demonstrated that the High line lambs appeared to secrete significantly less GnRH than the Low line and that the pituitary glands of the High line were 5 fold more sensitive to GnRH than the Low line. Pituitary sensitivity encompasses a large number of variables, including gonadotrophe and GnRH receptor number, the intracellular events which follow receptor activation and the amount of releasable LH stored in the pituitary gland, the individual or combined effects of which could result in differences in pituitary sensitivity. Pituitary gonadotrophe number/size was studied indirectly as a function of pituitary gland weight. The pituitary glands obtained from the High line tended to be heavier than those obtained from the Low line, however this difference was not statistically significant. The pituitary glands of the High line were also found to contain significantly more GnRH receptors/mg of protein than the Low line. The importance of this difference with regard to pituitary sensitivity was questioned, however, following the demonstration that the between line difference in the magnitude of the LH response was maintained in vitro following either GnRH stimulated LH release or the direct stimulation of both the Ca^2+-calmodulin and Protein Kinase C second messenger systems. Examination of the pituitary stores of LH in the two lines demonstrated that the 5μg dose of GnRH used in the selection programme stimulated a maximal release of LH in both lines, and that the High line stored significantly greater quantities of releasable LH compared with the Low line. The results also indicated that the two lines may differ in their ability to synthesise LH in response to GnRH stimulation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available