The aim of the present study was to evaluate the effects of the administration of a potent non-steroidal aromatase inhibitor, anastrozole, on male reproductive function in adult rats. As anastrozole was to be administered via the drinking water, a preliminary study was undertaken in female rats and showed that this route of administration was effective in causing a major decrease in uterine weight (P<0.02). In an initial study in male adult rats, anastrozole (100 mg/l or 400 mg/l) was administered via the drinking water for a period of 9 weeks. Treatment with either dose resulted in a significant increase ( approximately 10%) in testis weight and increase in plasma FSH concentrations (P<0.01) throughout the 9 weeks. Mating was altered in both groups of anastrozole-treated rats, as they failed to produce copulatory plugs. Histological evaluation of the testes from anastrozole-treated rats revealed that spermatogenesis was grossly normal. In a more detailed study, adult rats were treated with 200 mg/l anastrozole via the drinking water for periods ranging from 2 weeks to 1 year. Plasma FSH and testosterone concentrations were increased significantly (P<0.001) during the first 19 weeks of treatment. However, LH concentrations were increased only at 19 weeks (P<0.001) in anastrozole-treated rats, and this coincided with a further increase in circulating and intratesticular testosterone concentrations (P<0.05). No consistent change in inhibin-B concentrations was observed during the study. Suppression of plasma oestradiol concentrations could not be demonstrated in anastrozole-treated animals, but oestradiol concentrations in testicular interstitial fluid were reduced by 18% (P<0.01). Mating was again inhibited by anastrozole treatment, but could be restored by s.c. injection of oestrogen, enabling demonstration that rats treated for 10 weeks or 9 months were still fertile. Testis weight was increased by 19% and 6% after treatment for 19 weeks and 1 year, respectively. Body weight was significantly decreased (P<0.01) by 19 weeks of anastrozole treatment; after 1 year the animals appeared to have less fat as indicated by a 27% decrease in the weight of the gonadal fat pad. The majority of anastrozole-treated animals had testes with normal spermatogenesis but, occasionally, seminiferous tubules showed abnormal loss of germ cells or contained only Sertoli cells. Ten percent of anastrozole-treated animals had testes that appeared to contain only Sertoli cells, and one rat had 'giant' testes in which the tubule lumens were severely dilated. Morphometric analysis of the normal testes at 19 weeks showed no difference in the number of Sertoli cells or germ cells, or the percentage volumes of the seminiferous epithelium, tubule lumens and interstitium between control and anastrozole-treated rats. On the basis of the present findings, oestrogen appears to be involved in the regulation of FSH secretion and testosterone production, and is also essential for normal mating behaviour in male rats. Furthermore, these data suggest that the brain and the hypothalamo-pituitary axis are considerably more susceptible than is the testis to the effects of an aromatase inhibitor. Anastrozole treatment has resulted in a model of brain oestrogen insufficiency.

This article has been cited by other articles:

				S. A. Hild, G. R. Marshall, B. J. Attardi, R. A. Hess, S. Schlatt, D. R. Simorangkir, S. Ramaswamy, S. Koduri, J. R. Reel, and T. M. Plant Development of l-CDB-4022 as a Nonsteroidal Male Oral Contraceptive: Induction and Recovery from Severe Oligospermia in the Adult Male Cynomolgus Monkey (Macaca fascicularis) Endocrinology, April 1, 2007; 148(4): 1784 - 1796. [Abstract] [Full Text] [PDF]

				S. H. Giordano and G. N. Hortobagyi Leuprolide Acetate Plus Aromatase Inhibition for Male Breast Cancer J. Clin. Oncol., July 20, 2006; 24(21): e42 - e43. [Full Text] [PDF]

				X. Li, L. Strauss, A. Kaatrasalo, A. Mayerhofer, I. Huhtaniemi, R. Santti, S. Makela, and M. Poutanen Transgenic Mice Expressing P450 Aromatase as a Model for Male Infertility Associated with Chronic Inflammation in the Testis Endocrinology, March 1, 2006; 147(3): 1271 - 1277. [Abstract] [Full Text] [PDF]

				W. Jin, K. Y. Arai, G. Watanabe, A. K. Suzuki, S. Takahashi, and K. Taya The Stimulatory Role of Estrogen on Sperm Motility in the Male Golden Hamster (Mesocricetus auratus) J Androl, July 1, 2005; 26(4): 478 - 484. [Abstract] [Full Text] [PDF]

				C. A Oliveira, G. A B Mahecha, K. Carnes, G. S Prins, P. T K Saunders, L. R Franca, and R. A Hess Differential hormonal regulation of estrogen receptors ER{alpha} and ER{beta} and androgen receptor expression in rat efferent ductules Reproduction, July 1, 2004; 128(1): 73 - 86. [Abstract] [Full Text] [PDF]

				X. Li, L. Strauss, S. Makela, T. Streng, I. Huhtaniemi, R. Santti, and M. Poutanen Multiple Structural and Functional Abnormalities in the P450 Aromatase Expressing Transgenic Male Mice Are Ameliorated by a P450 Aromatase Inhibitor Am. J. Pathol., March 1, 2004; 164(3): 1039 - 1048. [Abstract] [Full Text] [PDF]

				K. M. Robertson, L. O'Donnell, E. R. Simpson, and M. E. E. Jones The Phenotype of the Aromatase Knockout Mouse Reveals Dietary Phytoestrogens Impact Significantly on Testis Function Endocrinology, August 1, 2002; 143(8): 2913 - 2921. [Abstract] [Full Text] [PDF]

				C. A. Oliveira, Q. Zhou, K. Carnes, R. Nie, D. E. Kuehl, G. L. Jackson, L. R. Franca, M. Nakai, and R. A. Hess ER Function in the Adult Male Rat: Short- and Long-Term Effects of the Antiestrogen ICI 182,780 on the Testis and Efferent Ductules, without Changes in Testosterone Endocrinology, June 1, 2002; 143(6): 2399 - 2409. [Abstract] [Full Text] [PDF]

				C. A. Oliveira, K. Carnes, L. R. Franca, and R. A. Hess Infertility and Testicular Atrophy in the Antiestrogen-Treated Adult Male Rat Biol Reprod, September 1, 2001; 65(3): 913 - 920. [Abstract] [Full Text] [PDF]

				T. R. Pak, G. R. Lynch, and P.-S. Tsai Testosterone and Estrogen Act via Different Pathways to Inhibit Puberty in the Male Siberian Hamster (Phodopus sungorus) Endocrinology, August 1, 2001; 142(8): 3309 - 3316. [Abstract] [Full Text] [PDF]

				L. O'Donnell, K. M. Robertson, M. E. Jones, and E. R. Simpson Estrogen and Spermatogenesis Endocr. Rev., June 1, 2001; 22(3): 289 - 318. [Abstract] [Full Text] [PDF]

				N. Mauras Author's Response: Aromatase Inhibitors in Pubertal Boys--Clinical Implications J. Clin. Endocrinol. Metab., April 1, 2001; 86(4): 1837 - 1838. [Full Text]

				F. J. Hayes, S. DeCruz, S. B. Seminara, P. A. Boepple, and W. F. Crowley Jr. Differential Regulation of Gonadotropin Secretion by Testosterone in the Human Male: Absence of a Negative Feedback Effect of Testosterone on Follicle-Stimulating Hormone Secretion J. Clin. Endocrinol. Metab., January 1, 2001; 86(1): 53 - 58. [Abstract] [Full Text]

				N. Atanassova, C. McKinnell, K. J. Turner, M. Walker, J. S. Fisher, M. Morley, M. R. Millar, N. P. Groome, and R. M. Sharpe Comparative Effects of Neonatal Exposure of Male Rats to Potent and Weak (Environmental) Estrogens on Spermatogenesis at Puberty and the Relationship to Adult Testis Size and Fertility: Evidence for Stimulatory Effects of Low Estrogen Levels Endocrinology, October 1, 2000; 141(10): 3898 - 3907. [Abstract] [Full Text] [PDF]