In vitro metabolism of androgens by mammalian cauda epididymal spermatozoa

Rajalakshmi, M.; Leask, J.T.S.; Waites, G. M. H.

doi:10.1016/s0039-128x(78)80040-3

Cited by 12 publications

(2 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Rabbit testes have been shown to secrete DHEA and to convert it to testosterone and testosterone precursors (42). Rabbit spermatozoa also can metabolize DHEA to 5-a-androstane-3,17-dione and 4-androstene-3, 17-dione, which can be converted to other androgens and estrogens (43). Weekly intramuscular injections of 17-alestradiol given to female New Zealand white rabbits fed a cholesterol and fat supplemented diet reduced the development of atherosclerosis (44,45).…”

Section: Discussionmentioning

confidence: 99%

Reduction of atherosclerosis by administration of dehydroepiandrosterone. A study in the hypercholesterolemic New Zealand white rabbit with aortic intimal injury.

Gordon¹,

Bush²,

Weisman

1988

J. Clin. Invest.

220

View full text Add to dashboard Cite

Dehydroepiandrosterone (DHEA) is an endogenous steroid that blocks carcinogenesis, retards aging, and exerts antiproliferative properties. In vitro, it is a potent inhibitor of glucose-6-phosphate dehydrogenase, the first committed step of the pentose phosphate pathway. In man, serum levels of DHEA and its sulfate peak in early adulthood and drop markedly with age. Epidemiologic evidence indicates that low levels of DHEA or its sulfate conjugate are linked to an increased risk of developing cancer or of death from cardiovascular disease. Like cancer, atherosclerosis is a proliferative process characterized by both initiation and promotion phases. This similarity provided a framework in which to study the antiatherogenic effects of DHEA.Rabbits were randomly assigned to four groups. Two groups of rabbits received aortic endothelial injury by balloon catheter and were fed a 2% cholesterol diet for 12 wk. DHEA, 0.5%, was incorporated into the diet of one group receiving the 2% cholesterol diet and endothelial injury and also into the diet of one of the control groups. Animals were killed after 12 wk and aortas, hearts, and livers were studied. Plasma samples were analyzed for total cholesterol, VLDL, LDL, HDL, triglycerides, DHEA, and DHEA-sulfate levels.The atherogenic insult resulted in severe atherosclerosis in animals not treated with DHEA. In those receiving DHEA there was an almost 50% reduction in plaque size (P = 0.006), inversely related to the serum level of DHEA attained. Fatty infiltration of the heart and liver were also markedly reduced. These beneficial actions were not attributable to differences in body weight gain, food intake, total plasma cholesterol or distribution of cholesterol among the VLDL, LDL, or HDL fractions.The results show that high levels of plasma DHEA inhibit the development of atherosclerosis and they provide an important experimental link to the epidemiologic studies correlating low DHEA-sulfate plasma levels with an enhanced risk of cardiovascular mortality.

show abstract

Section: Discussionmentioning

confidence: 99%

Reduction of atherosclerosis by administration of dehydroepiandrosterone. A study in the hypercholesterolemic New Zealand white rabbit with aortic intimal injury.

Gordon¹,

Bush²,

Weisman

1988

J. Clin. Invest.

220

View full text Add to dashboard Cite

show abstract

“…3,4 Information regarding the receptor-mediated action of DHEA is available only in caudal epididymal spermatozoa and activated human T lymphocytes. 7,8 On the other hand, it is well known that hormone replacement therapy with estradiol decreases the risk of coronary events in postmenopausal women. 9,10 An abundance of epidemiological data confirms this atheroprotective effect of estradiol 9 and has also prompted recommendations for the widespread use of estrogen replacement therapy for the primary prevention of ischemic cardiovascular disease in postmenopausal women.…”

mentioning

confidence: 99%

Dehydroepiandrosterone Retards Atherosclerosis Formation Through Its Conversion to Estrogen

Hayashi

Esaki

Muto

et al. 2000

ATVB

View full text Add to dashboard Cite

Abstract-Dehydroepiandrosterone (DHEA) is speculated to have an antiatherosclerotic effect, although the mechanism of action remains unclear. The objective of the current study was to determine whether the antiatherosclerotic effect of DHEA is related to its conversion to estrogen and to define the role of nitric oxide (NO) in the antiatherosclerotic effect of DHEA. Forty-eight oophorectomized rabbits were divided into 5 groups and fed the following diets for 10 weeks: group 1, a regular rabbit diet plus 1% cholesterol (a high-cholesterol diet [HCD]); group 2, an HCD plus 0.3% DHEA; group 3, an HCD plus 0.3% DHEA and fadrozole (2.0 mg ⅐ kg Ϫ1 ⅐ d Ϫ1 ), a specific aromatase inhibitor; group 4, an HCD plus 17␤-estradiol (20 g ⅐ kg Ϫ1 ⅐ d Ϫ1 ); and group 5, a regular diet. Atherosclerotic lesions, lipid deposition in aortic vessels, and basal and stimulated NO release were measured in the aforementioned groups of rabbits. NO release was measured by using an NO-selective electrode as well as by measuring vascular responses and the plasma NO metabolites nitrite and nitrate. The plasma total cholesterol level was increased, but there were no significant differences in lipid profile in the 4 groups of rabbits that were fed the HCD. The area occupied by atherosclerosis in the thoracic aorta was diminished by Ϸ60% in the DHEA-treated rabbits (group 2) compared with the HCD group of rabbits (group 1); there was a corresponding 80% decrease in the estradiol group (group 4) but only a 30% decrease in the DHEA plus fadrozole group (group 3). In the aortas of rabbits from groups 1 and 3, the acetylcholine-induced and tone-related basal NO-mediated relaxations were diminished compared with those of the controls (group 5). However, these relaxations were restored in the aortas of group 2 and 4 rabbits, and an increase in NO release was observed in groups 2 and 4 compared with groups 1 and 3, as measured by an NO-selective electrode. Injection of neither solvent (20% ethanol/distilled water) nor fadrozole significantly affected the atherosclerotic area or the NO-related responses described above. We conclude that Ϸ50% of the total antiatherosclerotic effect of DHEA was achieved through the conversion of DHEA to estrogen. NO may also play a role in the antiatherosclerotic effect of DHEA and 17␤-estradiol. have not yet been determined. In plasma, where the major portion of these hormones is present in the sulfate form, it is possible that DHEA-S serves as a reservoir for DHEA, since various tissues have been shown to contain steroid sulfatases. 1 The peak plasma levels of DHEA and DHEA-S occur at approximately age 25 years, decrease progressively thereafter, and diminish by 95% around the age of 85 years. Epidemiological evidence has shown that adult men with high plasma DHEA-S levels are less likely to die of cardiovascular disease. 2 A study indicated that administration of DHEA reduced aortic fatty streak formation and cholesterol accumulation by Ϸ30% to 40% in cholesterol-fed rabbits. 3 Another report has shown a 50% reduction...

show abstract

Secretion of Steroids by the Epididymis

Cooper

1986

The Epididymis, Sperm Maturation and Fertilisation

View full text Add to dashboard Cite

In vitro metabolism of androgens by mammalian cauda epididymal spermatozoa

Cited by 12 publications

References 29 publications

Reduction of atherosclerosis by administration of dehydroepiandrosterone. A study in the hypercholesterolemic New Zealand white rabbit with aortic intimal injury.

Reduction of atherosclerosis by administration of dehydroepiandrosterone. A study in the hypercholesterolemic New Zealand white rabbit with aortic intimal injury.

Dehydroepiandrosterone Retards Atherosclerosis Formation Through Its Conversion to Estrogen

Secretion of Steroids by the Epididymis

Contact Info

Product

Resources

About