Postejaculatory Increase of Prostatic Triiodothyronine (T3) Depends on Sympathetic Innervation in the Rat1

Abstract

Thyronines are essential for the development of the male reproductive system, including the prostate gland. Metabolically active 3,5,3' triiodothyronine (T(3)) is generated mainly by the extrathyroidal, enzymatic 5'deiodination of the prohormone thyroxine (T(4)), which is catalyzed by deiodinases type 1 (D1) and type 2 (D2). Prostate D1 activity is highly expressed during puberty and declines with age, but continuous, long-term sexual activity prevents this reduction. The aims of this study were to characterize the changes in prostatic D1 activity in response to consecutive ejaculations and to determine whether sympathetic input participates in the local T(3) generation (D1 activity). D1 activity was analyzed in prostates of sexually experienced, 4-mo-old male rats after one to five ejaculations. D1 activity, T(3) concentrations, and the T(3)-dependent gene ornithine decarboxylase (Odc) were measured after the fourth ejaculation in prostates of intact, sham, and sympathectomized (Smpx, hypogastric nerve) rats. D1 activity was evaluated by the radio-iodine-release method; T(3) was measured by radioimmunoassay and Odc expression by real-time PCR. Data showed a gradual increase of prostate D1 activity in response to consecutive ejaculations. The highest activity was found after the fourth ejaculation, and it decreased after the fifth. The increase of prostate D1 activity after ejaculation was blocked in Smpx males as compared to intact or sham animals. The changes in D1 activity correlate with prostatic T(3) concentrations and Odc expression. Circulating levels of T(3) were not affected by consecutive ejaculations or by Smpx. These findings indicate that the postejaculatory increase in prostatic generation of T(3) depends on sympathetic input.

Triiodothyronine Attenuates Prostate Cancer Progression Mediated by β-Adrenergic Stimulation

“…Mechanistically, it has been established that PKA activation and/or exchange protein activated by cAMP (EPAC) are crucial thyroid response (60). Tumor D1 activity was not measured, but previous studies have shown a direct correlation between enzyme activity (deiodination) and T3 generation in normal prostate tissue (35). T3 supplements also increased the expression of ARA70a, a prostate epithelium T3-responsive gene; ARA70 is reduced in prostate cancer cells, but its overexpression induces apoptosis and reduces the cell-invasive capacity (61).…”

“…In some carcinomas, thyroxine (T4) and triiodothyronine (T3) exert protumoral effects, stimulating cell proliferation and angiogenesis by nuclear (thyroid hormone receptors TRα and TRβ1) and/or nonnuclear mechanisms (αvβ3 integrin receptor/activation of MAPK and phosphoinositide 3-kinase [PI3K] pathways) (19)(20)(21)(22) analytical Methods RIA. Circulating levels of T3 were measured by homologous RIA as previously described (35). The assay contained serum or standards (0.1-4.0 ng T3/mL), hypothyroid serum, anti-T3 antibody (1:2,000) and 125 I-T3 (0.05 ng/mL) in a final volume of 350 μL.…”

Distribution of thyroid hormone and thyrotropin receptors in reproductive tissues of adult female rabbits

“…The localization of these receptors in the female prostate has not been previously described for any species. However, the presence of deiodinase type 1 and triiodothyronine in the prostate of male rats has been associated with the regulation of proliferation and secretion of epithelial cells (51)(52). Thus, similar functions of thyroid hormones and TSH could be expected for the female prostate.…”

Prostate gland as a target organ of thyroid hormones: advances and controversies

“…In addition, DIO1 activity is under endocrine control; it is stimulated by T4, estrogens, and prolactin (PRL) and is negatively regulated by androgens ( 11 ). An association between enzymatic activity and prostatic T3 levels was observed during different physiological challenges ( 12 , 13 ). Nevertheless, the contribution of DIO1 to T3 generation has been questioned in recent years, and instead, it has been suggested that this enzyme contributes to iodine recycling ( 1 , 2 ).…”

“…On the other hand, it has been shown that the sympathetic input activated by sexual behavior increases prostate DIO1 activity after consecutive ejaculations ( 13 ). In addition, DIO1 activity is under endocrine control; it is stimulated by T4, estrogens, and prolactin (PRL) and is negatively regulated by androgens ( 11 ).…”