The hypothalamic–hypophyseal–gonadal regulation of hepatic glutathione S-transferases in the rat

Abstract

Hepatic glutathione S-transferase activities were determined with the substrates 1,2-dichloro-4-nitrobenzene and 1-chloro-2,4-dinitrobenzene. Sexual differentiation of glutathione S-transferase activities is not evident during the prepubertal period, but glutathione conjugation with 1,2-dichloro-4-nitrobenzene is 2-3-fold greater in adult males than in females. Glutathione conjugation with 1-chloro-2,4-dinitrobenzene is slightly higher in adult males than adult females. No change in activity was observed after postpubertal gonadectomy of males or females. Neonatal castration of males results in a significant decrease in glutathione conjugation with 1,2-dichloro-4-nitrobenzene. Hypophysectomy, or hypophysectomy followed by gonadectomy did result in significantly higher glutathione S-transferase activities in both sexes. These increases can be reversed by implanting an adult male or female pituitary or four prepubertal pituitaries under the kidney capsule. Postpubertal sexual differentiation of glutathione S-transferase activities is neither dependent on pituitary sexual differentiation nor pituitary maturation. Prolactin concentrations are inversely related to glutathione S-transferase activities in hypophysectomized rats with or without ectopic pituitaries. Somatotropin exogenously administered to hypophysectomized rats results in decreased glutathione S-transferase activities, whereas prolactin has no effect. Adult male rats treated neonatally with monosodium l-glutamate to induce arcuate nucleus lesions of the hypothalamus have decreased glutathione S-transferase activities towards 1,2-dichloro-4-nitrobenzene and decreased somatotropin concentrations. Our experiments suggests that sexual differentiation of hepatic glutathione S-transferase is a result of a hypothalamic inhibiting factor in the male (absent in the female). This postpubertally expressed inhibiting factor acts on the pituitary to prevent secretion of a pituitary inhibiting factor (autonomously secreted by the female), resulting in higher glutathione S-transferase activities in the adult male than the adult female.

Further characterization of hormonal regulation of glutathione transferase in rat liver and adrenal glands. Sex differences and demonstration that growth hormone regulates the hepatic levels

“…It has, however, been reported that the activities of GSTs vary during development in the rat and mouse [12,13] and that these enzymes are regulated by sex hormones [13,14]. A sexual di-morphism in the isoenzyme pattern of cytosolic GSTs [15] and in activities towards several substrates such as CDNB and 1,2dichloro-4-nitrobenzene (DCNB) [16] has been observed in rat liver. A regulatory mechanism involving the pituitary has also been demonstrated both in the liver and the adrenal by ourselves [17] and by others [16].…”

“…A sexual di-morphism in the isoenzyme pattern of cytosolic GSTs [15] and in activities towards several substrates such as CDNB and 1,2dichloro-4-nitrobenzene (DCNB) [16] has been observed in rat liver. A regulatory mechanism involving the pituitary has also been demonstrated both in the liver and the adrenal by ourselves [17] and by others [16]. We found increased levels of several GSTs in both these organs after hypophysectomy.…”

Immunohistochemical distribution of isoenzymes of glutathione transferase in adult rat adrenal gland before and after hypophysectomy

“…Although these proteins can be induced by xenobiotics such as 3-methylcholanthrene, phenobarbital and trans-stilbene oxide in the liver, such induction does not seem to occur in the adrenal [7,5]. Hormonal regulation of glutathione transferases in several organs, including the adrenal, is, however, known to occur [18][19][20]. In a previous study we have shown increased levels of several of these isoenzymes in the rat adrenal in response to hypophysectomy [6].…”

Neonatal diethylstilbestrol treatment alters aflatoxin B1‐DNA adduct concentrations in adult rats

“…Apparently, DES females as well as the other treatment groups respond adequately to cytochrome P-450 and P-448 inducers to be equally capable of metabolizing and disposing of the procarcinogen, AFB1. Hence, altered imprinting of metabolism such as evidenced by altered endocrine secretions (25,34), enzyme levels (25-27/34), and carcinogen-DNA adduct levels can be modulated by activational mechanisms (27,41).…”