Increased Plasma Testosterone in Streptozotocin-Diabetic Female Rats*

Leaming, A.B.; Mathur, Rajesh S.; Levine, Jon H.

doi:10.1210/endo-111-4-1329

Cited by 26 publications

(13 citation statements)

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“…26 Studies have shown that the rat plasma T content remains elevated up to 4 weeks in diabetic rats following STZ induction. 27 Subsequent decline in plasma T was noted only beyond 120 to 140 days in diabetic rat. 28 The increase in the T content noted in the rat testis in our study is therefore a reflection of the STZ effect in the experimental diabetic rats used for the study.…”

Section: Discussionmentioning

confidence: 96%

A Phytooxysterol, 28-Homobrassinolide Modulates Rat Testicular Steroidogenesis in Normal and Diabetic Rats

et al. 2013

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Steroidogenesis in testicular cells depends upon the availability of cholesterol within testicular mitochondria besides the activities of 3b-hydroxysteroid dehydrogenase (3b-HSD, 17b-hydroxysteroid dehydrogenase [17b-HSD]), and the tissue levels of steroidogenic acute regulatory protein (StAR), androgen-binding protein (ABP), and testosterone (T). Cellular cholesterol biosynthesis is regulated by endogenous oxycholesterols acting through nuclear hormone receptors. Plant oxysterols, such as 28-homobrassinolide (28-HB), available to human through diet, was shown to exhibit antihyperglycemic effect in diabetic male rat. Its role in rat testicular steroidogenesis and lipid peroxidation (LPO) was therefore assessed using normal and streptozotocin-induced diabetic male rats. Administration of 28-HB (333 mg/kg body weight) by oral gavage for 15 consecutive days to experimental rats diminished LPO, increased antioxidant enzyme, 3b-HSD and 17b-HSD activities, and elevated StAR and ABP expression and T level in rat testis. We report that 28-HB induced steroidogenesis in normal and diabetic rat testis.

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Section: Discussionmentioning

confidence: 96%

A Phytooxysterol, 28-Homobrassinolide Modulates Rat Testicular Steroidogenesis in Normal and Diabetic Rats

et al. 2013

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“…Presumptive abnormalities of both pituitary and gonadal function have been described in vivo (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). However, the interpretation of these observations is limited by confounding influences of weight loss, protein catabolism, hyperglycemia, gonadal vasculopathy, and homeostatic responses of the pituitary-gonadal and adrenal axes in intact animals (15)(16)(17)(18)(19)(20)(21)(22). Moreover, precise cellular or biochemical alterations responsible for gonadal dysfunction in diabetes mellitus have not been delineated.…”

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confidence: 99%

Mechanisms subserving the trophic actions of insulin on ovarian cells. In vitro studies using swine granulosa cells

Veldhuis¹,

Kolp²,

Toaff³

et al. 1983

J. Clin. Invest.

108

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A B S T R A C T Direct actions of insulin on gonadal tissues have been difficult to demonstrate in vivo. We have developed an in vitro system in which swine ovarian cells remain highly responsive to trophic actions of insulin. Purified porcine insulin significantly augmented the biosynthesis and secretion of progesterone by cultured granulosa cells. These stimulatory actions of insulin were dose-and time-dependent and saturable. Under serum-restricted conditions, insulin also significantly amplified the capacity of estradiol and 8-bromo cyclic AMP to stimulate progesterone production. Inhibitors of protein and RNA synthesis (cycloheximide, actinomycin D, and alpha-amanatin) inhibited insulin action. The stimulation of progesterone production by insulin was attributable to increased biosynthesis of pregnenolone, rather than diminished catabolism of progesterone to its principal metabolite, 20a-hydroxypregn-4-en-3-one. Insulin also enhanced progesterone production in the presence of a soluble sterol substrate, 5-cholesten-3j3,25-diol, which readily gains access to the mitochondrial cholesterol side-chain cleavage system. Moreover, exposure of granulosa cells to insulin produced a three-to sevenfold increase in mitochondrial content of cytochrome P-450 measured by difference spectroscopy, with a corresponding increase in mitochondrial cholesterol side-chain cleavage activity.The capacity of insulin to facilitate progesterone biosynthesis by ovarian cells was mimicked by the insulinlike somatomedin, multiplication stimulating activity, but not by epidermal growth factor, fibroblast growth factor, or porcine relaxin. Insulin's augmentation of progesterone production reflected a selective action on progestin biosynthesis, since insulin significantly suppressed estrogen biosynthesis by granulosa cells.Thus, our investigations indicate that insulin acts on ovarian cells selectively to stimulate pregnenolone (but not estrogen) biosynthesis. The actions of insulin are exerted by processes that require protein and RNA synthesis, and by mechanisms that augment mitochondrial cytochrome P-450 content and facilitate the utilization of cholesterol in the side-chain cleavage 1046 J. Clin. Invest.

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“…These rats have adrenal hypertrophy with high resting levels of plasma corticosterone and an increased response to stress with changes in the feedback response [20]. More recently, Learning et al [6] have shown that the increase in serum testosterone that we had observed in diabetes [21 was due to increased production of androgens by the adrenals. The role of testosterone as a regulator of PRL receptors in rat liver is well documented [7][8][9][10][11].…”

Section: Discussionmentioning

confidence: 64%

“…In an earlier study, we observed that the loss of PRL receptors in diabetes was accompanied by an increase in serum testosterone, which returned to normal levels with insulin treatment [2]. Subsequently Learning et al [6], investigating steroid metabolism in female rats made diabetic with alloxan or streptozotocin, confirmed that diabetes increased testosterone levels. Whereas ovariectomy had no effect on testosterone levels in diabetes, adrenalectomy prevented the rise caused by diabetes, implying that the testosterone was of adrenal origin [6].…”

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confidence: 79%

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Adrenal involvement in the diabetes-induced loss of growth hormone and prolactin receptors in the livers of female rats

Bryson

Baxter

1986

Diabetologia

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Summary. Streptozotocin-induced diabetes causes a decrease in growth hormone and prolactin receptors in the livers of female rats, and in the serum concentration of somatomedin-C/ insulin-like growth factor-I, concomitantly with an increase in the serum testosterone levels. In this study, a possible role for adrenal androgens in the loss of receptors was examined. Rats were adrenalectomised bilaterally 3 days after the induction of diabetes with streptozotocin (100mg/kg intravenously), and livers were removed 3 days later. Adrenalectomy had no effect on binding of ovine prolactin or bovine growth hormone to liver microsomal membranes from non-diabetic rats, but in diabetic rats it entirely abolished the 56% decrease in prolactin binding and significantly reversed the 66% decrease in growth hormone binding and the parallel fall in serum levels of somatomedin-C/insulin-like growth factor-I (p<0.05). Adrenalectomy also prevented the diabetes-induced rise in serum testosterone. Daily injection of testosterone to normal and diabetic rats for 12 days significantly reduced both prolactin and growth hormone binding (p< 0.001), with the effect of diabetes being additive upon the testosterone effect. Implantation of testosterone-filled silastic capsules at the time of adrenalectomy (i. e. for 3 days) did not prevent the adrenalectomy-induced restoration of both growth hormone and prolactin receptors. The resulting high serum testosterone level did not reduce binding to growth hormone receptors in control rats over the 3 day period, and caused no further decrease in diabetic rats. However, binding to prolactin receptors was reduced by 47% in control animals with no further loss in diabetic animals (p < 0.001). Adrenalectomy prevented the loss of prolactin receptors in both testosterone-treated and diabetic rats. These results indicate that, whether or not the rise in testosterone of adrenal origin contributes to the receptor loss in diabetes, the effect also depends on another factor of adrenal origin.

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Increased Plasma Testosterone in Streptozotocin-Diabetic Female Rats*

Cited by 26 publications

References 0 publications

A Phytooxysterol, 28-Homobrassinolide Modulates Rat Testicular Steroidogenesis in Normal and Diabetic Rats

A Phytooxysterol, 28-Homobrassinolide Modulates Rat Testicular Steroidogenesis in Normal and Diabetic Rats

Mechanisms subserving the trophic actions of insulin on ovarian cells. In vitro studies using swine granulosa cells

Adrenal involvement in the diabetes-induced loss of growth hormone and prolactin receptors in the livers of female rats

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