Access Type

Open Access Dissertation

Date of Award

1-1-1998

Degree Type

Dissertation

Degree Name

Ph.D.

Department

Physiology

First Advisor

David M. Lawson, Ph.D.

Second Advisor

Marappa G. Subramanian, Ph.D.

Abstract

Purpose: The goal of this proposed research project was to demonstrate the adverse effects of cocaine on male fertility and to identify the mechanisms of action of cocaine on testicular function. Materials and Methods: Peripubertal male rats were given cocaine hydrochloride (15 mg./kg body weight, corresponding to an average single dose for a heavy cocaine user) either daily or twice weekly for more than 100 days. The fertility rate and the effect of cocaine on spermatogenesis were assessed by quantitative and qualitative methods. [3H] cocaine binding was measured on crude membrane from the testis using the method described by Madras et. Al. (67) with modifications. A testicular blood flow study was conducted after percutaneous injection of 30 mg./kg body weight cocaine using Xenon-133 washout study. The expression of androgen-binding protein and transferrin expression was evaluated using immunohistochemistry. Results: After 100 days of treatment with cocaine, the rats receiving daily cocaine had a pregnancy rate of only 33% versus 86% for controls (p<0.05). Morphometric analysis showed significant difference between the cocaine-treated groups and their respective controls. In this study we demonstrated that testicular tissue has receptor protein that binds [3H] cocaine saturably and specifically. Xenon-133 washout studies showed prolonged reduction in blood flow to the testes after cocaine administration and this effect was most pronounced at 15 minutes. Expression of transferrin and androgen-binding protein was significantly decreased in rats exposed to cocaine for 10 days. Conclusions: Chronic cocaine administration to peripubertal rats has profound adverse effects on fertility and spermatogenesis. For the first time we established cocaine binding sites in the testes. There was a significant reduction in the blood flow to the testes after cocaine administration, suggesting that one of the actions of cocaine may be due to vasoconstriction. The decreased expression of androgen-binding protein and transferrin demonstrates its adverse effects on Sertoli cell function.

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