Date of Award
Doctor of Philosophy
The corpus luteum in rabbits contains an adenylyl cyclase system that is responsive to both LH and catecholamines. Earlier studies have shown that exposure of corpora lutea to LH/hCG or catecholamines leads to desensitization of the adenylyl cyclase system, but the mechanism of desensitization by these hormones is unknown. Hormone receptors, G-proteins and the catalytic unit, are the primary components of the adenylyl cyclase system. In order to understand the mechanism of desensitization by LH and epinephrine, changes in luteal cyclase activity and components, after injection of either 100 IU hCG and or 2.5 mg/Kg epinephrine to pseudopregnant rabbits were studied. Adenylyl cyclase activity was determined in the presence or absence of oLH, ISO, NaF and forskolin. Both LH- and beta-adrenergic receptors were assayed by Scatchard analysis. Changes in G[subscript] s activity were assessed by the ability of cholate extracts of luteal membranes to reconstitute NaF- and ISO-stimulable adenylyl cyclase activity in S49 cyc-membranes. Changes in G[subscript] s and G[subscript] i-like protein were determined by utilizing the ability of cholera and pertussis toxins to specifically ADP-ribosylate these proteins. The results of these studies demonstrate that hormone-induced desensitization of rabbit luteal cyclase involves a loss in stimulable adenylyl cyclase activity, reduction in the number and or affinity of receptors, and G-protein alteration. hCG treatment results in homologous followed by heterologous desensitization, whereas epinephrine treatment results in heterologous desensitization. The present study demonstrates that hCG- and epinephrine-induced desensitization involves a complex series of interactions which results in altered receptor and G-protein function which in turn are responsible for the altered hormonal responsiveness observed after hormone treatment.
Digital Repository @ Iowa State University, http://lib.dr.iastate.edu/
Bhanu Pratap Jena
Jena, Bhanu Pratap, "Desensitization of the adenylyl cyclase system in the rabbit corpus luteum " (1988). Retrospective Theses and Dissertations. 8853.