Testosterone-dependent restoration of spermatogenesis in adult rats is impaired by a 5alpha-reductase inhibitor. 1999

L O'Donnell, and K Pratis, and P G Stanton, and D M Robertson, and R I McLachlan
Prince Henry's Institute of Medical Research, Clayton, Victoria, Australia.

Germ cell development (spermiogenesis in particular) in the adult rat is known to be testosterone dependent. Recently we proposed a role for the 5alpha reduction of testosterone to dihydrotestosterone (DHT) in the short-term restoration of round spermatid maturation when testicular testosterone levels are experimentally lowered. The current study aimed to further characterize the involvement of 5alpha-reductase in the restoration of spermatogenesis by investigating the short- and long-term restoration of specific germ cell populations by testosterone in the presence or absence of a 5alpha-reductase inhibitor (L685,273). Spermatogenesis in adult rats was suppressed for 8 weeks using 3-cm testosterone and 0.4-cm estradiol silastic implants (testosterone-estradiol [TE] treatment); spermatogenesis was then restored by administration of increasing doses of testosterone with or without a competitive 5alpha-reductase inhibitor or with the androgen receptor antagonist flutamide. Animals were then killed after either 4 days or 6 weeks of treatment so that we could study the short- and long-term restorations of spermatogenesis. Stereological analysis showed that germ cell development between late pachytene spermatocytes to round spermatids in stage VII during either short- or long-term restoration was not affected by 5alpha-reductase inhibition, but it was affected by flutamide. The conversion of round spermatids between stages VII and VIII was restored by testosterone treatment, but this restoration was prevented by flutamide. Both the short- and long-term restorations of this midspermiogenic event were significantly decreased when 5alpha-reductase was inhibited. After long-term restoration of spermatogenesis, elongated spermatids were restored to 42% of control but were significantly suppressed to 20% of control by coadministration of the 5alpha-reductase inhibitor because of a reduction in the number of round spermatids progressing between stages VII and VIII. The results demonstrate that the 5alpha-reduction of testosterone is particularly important for progression through midspermiogenesis, because this phase of germ cell development is more sensitive to withdrawal of androgens. We suggest that testicular 5alpha-reductase activity is important for the restoration or maintenance of low levels of sperm production in a hormonally based contraceptive setting.

UI MeSH Term Description Entries
D007986 Luteinizing Hormone A major gonadotropin secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Luteinizing hormone regulates steroid production by the interstitial cells of the TESTIS and the OVARY. The preovulatory LUTEINIZING HORMONE surge in females induces OVULATION, and subsequent LUTEINIZATION of the follicle. LUTEINIZING HORMONE consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH and FSH), but the beta subunit is unique and confers its biological specificity. ICSH (Interstitial Cell Stimulating Hormone),Interstitial Cell-Stimulating Hormone,LH (Luteinizing Hormone),Lutropin,Luteoziman,Luteozyman,Hormone, Interstitial Cell-Stimulating,Hormone, Luteinizing,Interstitial Cell Stimulating Hormone
D008297 Male Males
D008540 Meiosis A type of CELL NUCLEUS division, occurring during maturation of the GERM CELLS. Two successive cell nucleus divisions following a single chromosome duplication (S PHASE) result in daughter cells with half the number of CHROMOSOMES as the parent cells. M Phase, Meiotic,Meiotic M Phase,M Phases, Meiotic,Meioses,Meiotic M Phases,Phase, Meiotic M,Phases, Meiotic M
D009929 Organ Size The measurement of an organ in volume, mass, or heaviness. Organ Volume,Organ Weight,Size, Organ,Weight, Organ
D011467 Prostate A gland in males that surrounds the neck of the URINARY BLADDER and the URETHRA. It secretes a substance that liquefies coagulated semen. It is situated in the pelvic cavity behind the lower part of the PUBIC SYMPHYSIS, above the deep layer of the triangular ligament, and rests upon the RECTUM. Prostates
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D005640 Follicle Stimulating Hormone A major gonadotropin secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Follicle-stimulating hormone stimulates GAMETOGENESIS and the supporting cells such as the ovarian GRANULOSA CELLS, the testicular SERTOLI CELLS, and LEYDIG CELLS. FSH consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. FSH (Follicle Stimulating Hormone),Follicle-Stimulating Hormone,Follitropin
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013091 Spermatogenesis The process of germ cell development in the male from the primordial germ cells, through SPERMATOGONIA; SPERMATOCYTES; SPERMATIDS; to the mature haploid SPERMATOZOA. Spermatocytogenesis,Spermiogenesis
D013737 Testis The male gonad containing two functional parts: the SEMINIFEROUS TUBULES for the production and transport of male germ cells (SPERMATOGENESIS) and the interstitial compartment containing LEYDIG CELLS that produce ANDROGENS. Testicles,Testes,Testicle

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