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Intercellular Communication Between Sertoli Cells and Leydig Cells in the Absence of Follicle-Stimulating Hormone-Receptor Signaling¹

^a Molecular Reproduction Research Laboratory, Clinical Research Institute of Montreal, Montreal, Quebec, Canada H2W 1R7

ABSTRACT

Effective interactions among the various compartments of the testis are necessary to sustain efficiency of the spermatogenic process. To study the intercellular communication between the Sertoli and Leydig cells in the complete absence of FSH receptor signaling, we have examined several indices of Leydig cell function in FSH receptor knockout (FORKO) mice. The serum testosterone levels were reduced in the 3- to 4-mo-old adult FORKO males compared to wild-type mice despite no significant alteration in circulating LH levels. Treatment with ovine LH resulted in a dose-dependent increase in serum testosterone levels in all three genotypes (+/+, +/-, and -/-). However, the response in FORKO males was significantly reduced. Similarly, the total intratesticular testosterone per testis was also lower, but the intratesticular testosterone per milligram of testis was significantly elevated in the FORKO males. Western blot analysis revealed an apparent higher expression of the enzyme 3ß-hydroxysteroid dehydrogenase (3ß-HSD) as well as LH-receptor density in the testis of FORKO males. Immunohistochemistry also showed an increase in the intensity of 3ß-HSD staining in the testicular sections of FORKO males. Although LH receptor binding increased per unit weight in FORKO mice, the total LH binding remained the same in all genotypes. Taken together, the results of the present study suggest that, in the absence of FSH receptor signaling, the testicular milieu is altered to affect Leydig cell response to LH such that circulating testosterone is reduced in the adult mutant. Studies are currently under way to understand the mechanisms underlying this phenomenon.

FOOTNOTES

First decision: 4 April 2001.

¹ Supported by the Medical Research Council of Canada and the Canadian Institutes of Health Research (CIHR). N.D. is a recipient of a doctoral award from the CIHR.

² Correspondence: M. Ram Sairam, Molecular Reproduction Research Laboratory, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, PQ, Canada H2W 1R7. FAX: 514 987 5585; sairamm{at}ircm.qc.ca

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