RESUMEN
Testosterone (T) synthesised in Leydig cells enters the epididymis and may there be converted into dihydrotestosterone (DHT) by 5α-reductase (5α-red) or into 17ß-oestradiol (E2) by P450 aromatase (P450-aro). D-aspartate (D-Asp) is known to induce T synthesis in the testis. In this study, we investigated the effects of in vivo D-Asp administration in two major regions of the rat epididymis (Region I: initial segment, caput, corpus; Region II: cauda). The results suggest that exogenous D-Asp was taken up by both regions of rat epididymis. D-Asp administration induced a rapid increase in T, followed by a more gradual decrease in the T:DHT ratio in Region I. In Region II, T levels rapidly decreased and the T:DHT ratio was consistently lower relative to the control. Expression of 5α-red and androgen receptor genes showed a good correlation with DHT levels in both regions. D-Asp treatment also induced an increase of both E2 levels and oestradiol receptor-α (ERα) expression in Region I, whereas neither E2 levels nor ERα expression were affected in Region II. The early increase of P450-aro expression in Region I and late increase in Region II suggests a direct involvement of D-Asp modulation in P450-aro gene expression. Our results suggest that D-Asp modulates androgen and oestrogen levels and expression of androgen and oestrogen receptors in the rat epididymis by acting on the expression of 5α-red and P450-aro genes.
Asunto(s)
Ácido D-Aspártico/farmacología , Dihidrotestosterona/metabolismo , Epidídimo/efectos de los fármacos , Estrógenos/metabolismo , Testosterona/metabolismo , 3-Oxo-5-alfa-Esteroide 4-Deshidrogenasa/metabolismo , Animales , Aromatasa/metabolismo , Epidídimo/fisiología , Estradiol/metabolismo , Masculino , Ratas , Receptores Androgénicos/metabolismoRESUMEN
The rat Harderian gland (HG) is an orbital gland producing a copious lipid secretion. Recent studies indicate that its secretory activity is regulated by thyroid hormones. In this study, we found that both isoforms of the thyroid hormone receptor (Trα (Thra) and Trß (Thrb)) are expressed in rat HGs. Although Thra is expressed at a higher level, only Thrb is regulated by triiodothyronine (T3). Because T3 induces an increase in lipid metabolism in rat HGs, we investigated the effects of an animal's thyroid state on the expression levels of carnitine palmitoyltransferase-1A (Cpt1a) and carnitine palmitoyltransferase-1B (Cpt1b) and acyl-CoA oxidase (Acox1) (rate-limiting enzymes in mitochondrial and peroxisomal fatty acid oxidation respectively), as well as on the mitochondrial compartment, thereby correlating mitochondrial activity and biogenesis with morphological analysis. We found that hypothyroidism decreased the expression of Cpt1b and Acox1 mRNA, whereas the administration of T3 to hypothyroid rats increased transcript levels. Respiratory parameters and catalase protein levels provided further evidence that T3 modulates mitochondrial and peroxisomal activities. Furthermore, in hypothyroid rat HGs, the mitochondrial number and their total area decreased with respect to the controls, whereas the average area of the individual mitochondrion did not change. However, the average area of the individual mitochondrion was reduced by â¼50% in hypothyroid T3-treated HGs, and the mitochondrial number and the total area of the mitochondrial compartment increased. The mitochondrial morphometric data correlated well with the molecular results. Indeed, hypothyroid status did not modify the expression of mitochondrial biogenesis genes such as Ppargc1a, Nrf1 and Tfam, whereas T3 treatment increased the expression level of these genes.