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1 November 2004 Testicular Phenotype in Luteinizing Hormone Receptor Knockout Animals and the Effect of Testosterone Replacement Therapy
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The LH receptor knockout model, developed in our laboratory, was used in determining what FSH alone can do in the absence of LH signaling and whether any of the testicular LH actions are not mediated by androgens. The results revealed that null animals contained smaller seminiferous tubules, which contained the same number of Sertoli cells, spermatogonia, and early spermatocytes as wild-type siblings. The number of late spermatocytes, on the other hand, was moderately decreased, the number of round spermatids was dramatically decreased, and elongated spermatids were completely absent. These changes appear to be due to an increase in apoptosis in spermatocytes. While the number of Leydig cells progressively increased from birth to 60 days of age in wild-type animals, they remained unchanged in null animals. Consequently, 60-day-old null animals contained only a few Leydig cells of fetal type. The age-dependent increase in testicular macrophages lagged behind in null animals compared with wild-type siblings. Orchidopexy indicated that −/− testicular phenotype was not due to abdominal location. Rather, it was mostly due to androgen deficiency, as 21-day testosterone replacement therapy stimulated the growth of seminiferous tubules, decreased apoptosis, and increased the number of late spermatocytes and round spermatids and their subsequent differentiation into mature sperm. The therapy, however, failed to restore adult-type Leydig cells and testicular macrophage numbers to the wild-type levels. In summary, our data support the concept that FSH signaling alone can maintain the proliferation and development of Sertoli cells, spermatogonia, and early spermatocytes. LH actions mediated by testosterone are required for completion of spermatogenesis, and finally, androgen-independent actions of LH are required for the formation of adult-type Leydig cells and recruitment of macrophages into the testes.

Z. M. Lei, S. Mishra, P. Ponnuru, X. Li, Z. W. Yang, and ChV. Rao "Testicular Phenotype in Luteinizing Hormone Receptor Knockout Animals and the Effect of Testosterone Replacement Therapy," Biology of Reproduction 71(5), 1605-1613, (1 November 2004).
Received: 23 April 2004; Accepted: 1 July 2004; Published: 1 November 2004

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