Date of Award

6-1991

Degree Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

Department

Medical Sciences

Supervisor

E.V. YoungLai

Abstract

The aim of the present study was to characterize the pituitary GnRH binding site in the rabbit and investigate its possible role in sexual maturation of the female rabbit. A radioligand binding assay was established and the presence of specific ¹²⁵I-DAla⁶EA binding sites in the anterior pituitary gland of the rabbit was demonstrated. ¹²⁵I-DA1a⁶EA binding was saturable, specific, displaceable, reversible, correlated with increasing tissue concentrations and susceptible to physiological manipulation. Significant ¹²⁵I-DA1a⁶EA binding was not present in the rabbit ovary suggesting that GnRH or GnRH-related peptides are not directly involved in the control of luteal function of the rabbit. 12S1_DAla6EA binding indicated the presence of two binding sites in the female adult rabbit pituitary; a high affinity, low capacity site (Kd= 0.3-0.4 nM; Bmax = 100-200 fmol/mg protein) and a lower affinity, high capacity site (Kd= 30 nM; Bmax=5-8000 fmol/mg protein). Ontogeny of ¹²⁵I-DA1a⁶EA binding in the female rabbit (40 to 120 days of age) did not show a correlation between binding site number and serum LH. In addition, the net serum LH response in female rabbits to a subcutaneous injection of DA1a⁶EA (10ng, 100ng, 1μg per kg body weight) was not significantly different between animals 40, 75 and 120 days of age. This suggests that a decrease in pituitary responsiveness to GnRH is not associated with sexual maturation in the female rabbit. Results indicate that factors other than and/or in addition to GnRH binding site number, such as post-receptor events play a role in gonadotropin secretion in the female rabbit.


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