Estrogen metabolism in neural tissues of rabbits: 17β — Hydroxysteroid oxidoreductase activity

Reddy, V. R.

doi:10.1016/0039-128x(79)90049-7

Cited by 16 publications

(7 citation statements)

References 25 publications

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“…Oestradiol 17^-oxidoreductase in neural tissues of rats The present data demonstrating a system, which interconverts oestradiol and oestrone, expands our earlier observations in rabbits (Reddy et al 1974b;Reddy 1979). The tissues from females showed higher activity of oestradiol 17ß-oxidoreductase than males (Table 4).…”

Section: Catecholoestrogenformation In Neural Tissues Of Ratssupporting

confidence: 88%

“…The higher oestradiol 17ß-oxidoreductase activity in pituitary and hypothala¬ mus may suggest its importance in the regulation of endogenous levels of oestradiol in these tissues and control of neuroendocrine function. We have observed that the reaction catalyzed by the oestra¬ diol 17ß-oxidoreductase in neural tissues of rats favours the reduction of oestrone which is similar to rabbit neural tissues (Reddy 1979). The low levels of oestrone reduction in hypo¬ thalamus may in part be due to the hypothalamic neurons that are specific to oestrone (Luttge & Whalen 1970).…”

Section: Catecholoestrogenformation In Neural Tissues Of Ratsmentioning

confidence: 95%

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Oestrogen metabolism in adult rat's brain

Reddy¹,

Daly

1981

Acta Endocrinologica

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In vitro incubation of pituitary, hypothalamus and cerebral cortex with [3H]oestrogens revealed that the oestrogens are actively metabolized by these tissues. The covalent binding of oestrone and oestradiol to acid precipitable proteins was observed. Pituitary from male rats exhibited higher covalent binding of oestrogens than females. The 2-hydroxylation was found to be greater than 16-hydroxylation. Furthermore, male pituitary exhibited higher 2-hydroxylation of oestrogens than females. No such sexual dimorphism was observed in 16-hydroxylation. C17-reduction was found to be greater than oxidation in these tissues. Furthermore, the C17\ x=req-\ reduction in pituitary and hypothalamus from females was greater than males, which is in contradistinction to protein binding and 2-hydroxylation of oestrogens. In both male and female animals the pituitary was metabolically more active than hypothalamus and cortex. In addition, oestradiol was hydroxylated more than oestrone either at 2-or 16-positions. These results indicate that in central nervous system and pituitary the oestrogens are metabolized preferentially by 2-hydroxylation pathway and it is suggested that the in situ metabolism of oestrogens in neuroendocrine tissues may be important in the control of oestrogen effects on neuroendocrine function and sex behaviour.

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Section: Catecholoestrogenformation In Neural Tissues Of Ratssupporting

confidence: 88%

Section: Catecholoestrogenformation In Neural Tissues Of Ratsmentioning

confidence: 95%

Oestrogen metabolism in adult rat's brain

Reddy¹,

Daly

1981

Acta Endocrinologica

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“…In super natants from brain samples, 27% of the extractable radioac tivity was ['H]estrone while in supernatants from pituitary gland and peripheral tissues it accounted for only 16%. The activity of l7|3-hydroxysteroid oxidoreductase is consider ably higher in the pituitary gland than in the brain of rhesus monkeys [27], and our results might be explained by the fact that the equilibrium of the estradiol-estrone interconver sion catalyzed by this enzyme lies towards estradiol [23]. There is strong evidence in the male rat that estrogenic metabolites of testosterone produced by intracerebral aromatization mediate the effects of testosterone both on sexual differentiation of the brain during development [16] and on activation of sexual behavior in the adult [4,6,12].…”

Section: Discussionmentioning

confidence: 59%

[<sup>3</sup>H]Estradiol and Its Metabolites in the Brain, Pituitary Gland, and Reproductive Tract of the Male Rhesus Monkey

1986

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Previous studies have shown that [³H]estradiol is the major nuclear metabolite of [³H]testosterone in the hypothalamus, preoptic area and amygdala of the male rhesus monkey, and it has been proposed that some of the stimulatory effects of testosterone on male sexual behavior may be mediated by estradiol-concentrating neurons. To map these neurons and identify metabolites, 4 castrated male rhesus monkeys were each injected with 0.47 mCi/kg [³H]estradiol, and the brains were removed 60 min later. Left halves were frozen for thaw-mount autoradiography, and right halves were used to isolate cell nuclei from different brain regions. A fifth animal was used to validate the methodology. Radioactive steroids were identified and measured by high performance liquid chromatography. Brain areas previously shown to contain labeled neurons after [³H]testosterone administration were also labeled after [³H]estradiol, including medial preoptic nucleus (n.), anterior hypothalamic area, bed n. of stria terminalis, ventromedial n., premammillary n., and corticomedial amygdala. Some areas not labeled after [³H]testosterone were labeled after [³H]estradiol, including lateral septal n., arcuate n., paraventricular n., claustrum, entorhinal cortex, and spinal cord. The pars distalis of the pituitary gland was heavily labeled. Most (83%) of the radioactivity in cell nuclei was [³H]estradiol while [³H]estrone was a major metabolite (25%) in supernatants. In the brain, the highest nuclear concentration of [³H]estradiol was in the hypothalamus (249.2 ± 20.0 fmol/mg DNA), although in the previous experiments with [³H]testosterone, the highest nuclear concentrations of [³H]estradiol were found in the amygdala. We interpret these results to indicate that local metabolic differences in the brain may underlie some of the different behavioral effects of gonadal steroids in primates.

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“…the interconversion of oestrone and oestradiol has been demonstrated in a large number of mouse tissues (Milewich, Garcia & Gerrity, 1985), tissues of other animals (Bitar, Cochran & Warren, 1979;Reddy, 1979;Entenmann, Sierralta & Jungblut, 1980;Hartiala, Uotila & Nienstedt, 1980), and in vari¬ ous human tissues, e.g. endometrium (Tseng, Stolee & Gurpide, 1972), vaginal mucosa (Weinstein, Frost & Hsia, 1968), lung (Milewich, Hendricks & Romero, 1982), testis (Ryan & Engel, 1953), ileum (Ryan & Engel, 1953), skin (Weinstein et al 1968), liver (Breuer, Knuppen & Haupt, 1966), adipose tissue (Bleau, Roberts &Chapdelaine, 1974) and erythrocytes (Jacobsohn & Hochberg, 1968).…”

mentioning

confidence: 96%

Activity of 17β-hydroxysteroid oxidoreductase in tissues of the human fetus

Milewich¹,

MacDonald

Carr³

1989

Journal of Endocrinology

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The interconversion of oestrone and oestradiol, androstenedione and testosterone, and dehydroepiandrosterone and 5-androstene-3 beta,17 beta-diol in mammalian tissues is catalysed by 17 beta-hydroxysteroid oxidoreductase (17 beta-HSOR). To identify tissue sites of 17 beta-HSOR activity in the human fetus, microsomal fractions from 15 different fetal tissues obtained from first and second trimester pregnancies were used for evaluation of enzymatic activity by use of [17 alpha-3H] oestradiol as the substrate and NADP+ as the co-factor. With these reagents, the enzyme-catalysed reaction led to the production of both non-radiolabelled oestrone and NADP3H in equimolar amounts; the radioactivity associated with NADP3H was used to quantify 17 beta-HSOR activity. Activity of 17 beta-HSOR was present in microsomes of all the tissues evaluated. The specific activity of the enzyme was highest in liver and placental microsomes. The interconversion of oestradiol and oestrone in microsomal fractions of nine different fetal tissues was studied by the use of substrates labelled with tritium at stable nuclear positions ([6,7-3H]oestradiol and [6,7-3H]oestrone). The products, [3H]oestrone and [3H]oestradiol, were quantified by the use of established techniques; other metabolites formed in these incubations were not identified. The reductive pathway of metabolism (oestrone to oestradiol) appeared to be favoured in microsomal fractions prepared from placenta, fetal zone of the adrenal gland and, possibly, lung. The oxidative pathway (oestradiol to oestrone) appeared to be favoured in microsomes prepared from liver, intestine, stomach, kidney, brain and heart. 17 beta-HSOR activity in fetal liver also was assessed by the use of fresh and frozen-thawed tissue, homogenate, subcellular fractions, and, also, in primary hepatocytes maintained in culture; the specific activity of the enzyme was highest in the microsomal fraction of liver tissue and 17 beta-HSOR activity in liver microsomes was linear with time of incubation up to 1 h. In hepatocytes, the enzymatic activity was linear with time of incubation up to 2 h and with cell number up to 2.5 x 10(5) cells/ml; the apparent Michaelis constant of hepatocyte 17 beta-HSOR for oestradiol was 11 mumol/l. The specific activity of 17 beta-HSOR did not change after pretreatment of hepatocytes for 24 h with insulin, glucagon or dexamethasone.

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Estrogen metabolism in neural tissues of rabbits: 17β — Hydroxysteroid oxidoreductase activity

Cited by 16 publications

References 25 publications

Oestrogen metabolism in adult rat's brain

Oestrogen metabolism in adult rat's brain

[<sup>3</sup>H]Estradiol and Its Metabolites in the Brain, Pituitary Gland, and Reproductive Tract of the Male Rhesus Monkey

Activity of 17β-hydroxysteroid oxidoreductase in tissues of the human fetus

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