The aromatase activity from purified testicular sources (Leydig and Sertoli cells) of immature (5- and 15-day-old) and adult rats (60-day-old) was investigated by the tritiated water release method in isolated Leydig and Sertoli cells that were morphologically and functionally characterized. Electron micrographs of Sertoli cell preparations from different ages showed no marked changes, except that tight junctions between Sertoli cells normally present in 60-day-old rats were not observed in 5-day-old and rarely found in 15-day-old animals. Leydig cells underwent ultrastructural changes along with development, such as the appearance of thicker nuclear heterochromatin and laminar-like mitochondria. The 15-day-old rat interstitial tissue possessed less than 10% of Leydig cells morphologically similar to those present in the adult, whereas the rest were probably transition cells, since they did not show typical Leydig cell structure but were able to bind [125I]iodo-hCG, as evaluated by autoradiography. The number of LH/hCG-binding sites increased with age in Leydig cells, but was not detectable in Sertoli cells. The highest number of FSH-binding sites in Sertoli cells was observed in the 15-day-old animals. Minor FSH binding was found in Leydig cell preparations, which was consistent with the known LH contamination of the human FSH tracer preparation. cAMP production increased significantly in Leydig cells only after hCG treatment and in Sertoli cells after FSH stimulation. Both types of cells were shown to have the capacity for aromatization. The aromatase activity increased in the Leydig cell but decreased in the Sertoli cell during testicular development. The highest aromatase activity was found in adult rat Leydig cells, and the enzyme activity was significantly higher (2-fold) in purified Leydig cells than in crude interstitial cell preparations. Estradiol production in response to hCG stimulation in vitro was not different from the basal value in 5-day-old rat Leydig cells, but increased significantly in 60-day-old rat Leydig cells. In conclusion, 1) Leydig cells are the major site of estrogen synthesis in adult rat testis; and 2) the low aromatase activity observed in immature rat Leydig cells could partially explain the differential response of the mature and immature rat testis to hCG-induced desensitization.

Our data showed that Sal-T is a reliable marker of testosterone bioavailability. The results support the inclusion of this biomarker as a noninvasive approach in the diagnosis of male androgen deficiency.

Information on the effect of abnormal thyroid function on male reproduction is less available than that for the female. To assess the effects of hyperthyroidism on hypothalamic-pituitary-testicular axis and on spermogram parameters, 25 male patients (19-47 years old) suffering from active Graves' disease were studied. Serum luteinizing hormone (LH), follicle stimulating hormone (FSH), and prolactin (PRL) were measured before and after administration of 100 microg GnRH plus 200 microg thyrotropin-releasing hormone (TRH). Testosterone (T), estradiol (E2), and 17-hydroxyprogesterone (17-OHP) were determined before and after 5000 IU human chorionic gonadotropin (HCG) administration. Serum sex hormone-binding globulin (SHBG), cortisol-binding globulin (CBG), androstenedione and bioavailable testosterone (bioT), and bioavailable estradiol (bioE2) were also measured. Spermograms according to World Health Organization (WHO) criteria were determined in 21 patients. Hormonal and seminal studies were repeated in six patients after 7 to 19 months of euthyroidism achieved after treatment for hyperthyroidism. As a control group, 10 normal men were evaluated. Impaired sexual function, gynecomastia, and low testicular volume were found in 12, 6, and 3 hyperthyroid patients. Mean basal LH was significantly higher than the control group (7.8 +/- 4.7 vs. 5.0 +/- 1.9 mIU/mL, respectively, p < 0.02), with hyperresponse to GnRH. The response of PRL to TRH was lower in patients versus control group (30 minutes: 3.9 +/- 3.4 and 12.0 +/- 2.8 ng/mL, p < 0.01). Basal levels of steroids and SHBG were significantly higher in patients than in normal men (T: 9.3 +/- 3.3 vs. 5.4 +/- 1.6 ng/mL, p < 0.005; E2: 62.2 +/- 25.2 vs. 32.1 +/- 11.0 pg/mL, p < 0.005; 17-OHP: 2.4 +/- 0.9 vs. 1.1 +/- 0.5 ng/mL, p < 0.001; SHBG: 102.3 +/- 37.3 vs. 19.0 +/- 5.0 nmol/L, p < 0.01). The maximal increment of T and 17-OHP after HCG was lower in hyperthyroid patients than in normal men (p < 0.019 and p < 0.001, respectively). Basal bioT was lower in patients than controls (1.7 +/- 0.8 and 3.1 +/- 1.9 ng/mL, p < 0.02). The following incidence of abnormal semen parameters was found: asthenospermia 85.7%, hypospermia 61.9%, oligospermia 42.9%, necrospermia 42.9% and teratospermia 19.0%. In euthyroidism, a normalization of 85% of seminal alterations was observed in the limited number of patients evaluated. Our results confirm that hyperthyroidism causes marked alterations of the gonadotropic and PRL axis and dramatically affects spermatic function. BioT measurement was useful to identify hypoandrogenism in these patients in spite of the high concentration of total testosterone. The restoration of most semen parameters when euthyroidism was achieved suggests that the alterations were induced by the Graves' disease.

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