Morphometric evaluation of the hypothalamic-ovarian axis of the ketonuric, diabetic Chinese hamster: Relationship to the reproductive cycle

Garris, David R.; Smith, Carlton; Davis, Daniel; Diani, A. R.; Gerritsen, G. C.

doi:10.1007/bf00252855

Cited by 43 publications

(35 citation statements)

References 16 publications

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“…In the present study, the ability of E to stabilize systemic glucose levels and accentuate carbohydrate utilization in such steroid target sites as the amygdala, hypothalamus and septum [28]is of particular interest since these CNS loci participate in a variety of neuroendocrine regulatory functions [2]and have been recognized to possess glucoregulatory neurons [13, 29]. These findings support the observation that premature neuronal degeneration [5], which is recognized to occur with the exacerbation of the diabetic condition in this species, is pronounced in these CNS sites [5, 6, 7, 8, 9]. These studies suggest that estrogenic compounds may serve as regionally specific CNS metabolic stimulants with respect to such functions as neuronal carbohydrate metabolism in steroid-hormone-responsive loci of the CNS.…”

Section: Discussionsupporting

confidence: 77%

“…Alterations in neuronal structure, function and metabolism are recognized to occur in association with type I (insulin-dependent) and type II (non-insulin-dependent) diabetic conditions [1, 2, 3, 4, 5, 6, 7, 8, 9]. In the genetically obese-diabetic C57BL/KsJ (db/db) mouse [10, 11], premature neuronal degeneration [5, 12], depressed glucose uptake rates [13, 14, 15, 16], alterations in regional brain bioamine deposition [17, 18], impaired hypothalamic-pituitary regulation [19, 20, 21]and a decline in neuronal responsiveness to steroid hormones [19, 20, 22]occur in association with the expression of the hyperglycemic-hyperinsulinemic state in this murine model.…”

Section: Introductionmentioning

confidence: 99%

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Estrogenic Stimulation of Hypothalamic-Limbic System Metabolism in Ageing Diabetic C57BL/KsJ Mice

Garris

1999

Neuroendocrinology

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The therapeutic influences of estrogen treatment on age- and diabetes-related declines in regional brain glucose utilization (RBGU) rates were evaluated in 8- to 20-week-old female C57BL/KsJ normal (+/?) and diabetic (db/db) mice. Following either oil vehicle (oil: 0.1 ml) or estradiol (E: 1 µg/3.5 days) treatments starting at 3 weeks of age, RBGU rates were subsequently determined at 8, 12, 16 and 20 weeks of age. A gradual decline in the basal rate of brain glucose utilization was observed in all control (oil- and E-treated) groups between 8 and 20 weeks. Expression of the hyperglycemic-obese diabetes syndrome in db/db mice resulted in a significant reduction in RBGU rates between 8 and 20 weeks relative to control values. In estrogen-sensitive hypothalamic, septal and amygdaloid regions, E therapy modulated RBGU rates in db/db mice relative to oil-treated diabetics, but did not significantly alter utilization rates in +/? mice. In cortical samples, E therapy had no significant influence on glucose utilization rates in either control or diabetic groups. A noticeable pattern of maturation-associated decline in CNS glucose utilization rates in all brain regions resulted in comparable regional metabolic indices being exhibited by all groups at 20 weeks of age, with the exception of the diabetes-associated exacerbation of RBGU rates in the oil-treated db/db group. These data demonstrate that the normal development-related decline in regional brain carbohydrate metabolism is accelerated by the diabetes syndrome, and that E therapy can modulate the syndrome-associated suppression of glucose utilization in steroid-sensitive CNS loci. These data suggest that the depressive influences of the diabetes syndrome on brain carbohydrate utilization rates may be therapeutically modified in recognized CNS regions possessing steroid-sequestering, metabolically responsive neurons.

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Section: Discussionsupporting

confidence: 77%

Section: Introductionmentioning

confidence: 99%

Estrogenic Stimulation of Hypothalamic-Limbic System Metabolism in Ageing Diabetic C57BL/KsJ Mice

Garris

1999

Neuroendocrinology

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“…Indeed, the observation that ovulation in alloxantreated rats can be restored by repeated injections of LHRH on proestrus [4] is strong evidence of a hypothalamic failure. Furthermore, a hypothalamic defect in diabetes is also implied by the abnormal morphology of hypothalamic nuclei and the median eminence in diabetic Chinese hamsters [20] and in streptozotocin-treated male rats [21].…”

Section: Discussionmentioning

confidence: 99%

Feedback effects of steroids and gonatrophin control in adult rats with streptozotocin-induced diabetes mellitus

1985

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Summary. The effects of long-and short-term streptozotocininduced diabetes mellitus on the control of gonadotrophin secretion have been investigated in adult intact rats. A high dose of streptozotocin (80 mg/kg), administered intraperitoneally 3 days before experimentation, inhibited ovulation and reduced the pituitary luteinizing hormone response to luteinizing hormone releasing hormone in proestrous rats. A lower dose (40 mg/kg) did not inhibit ovulation but abolished the luteinizing hormone releasing hormone-priming effect on the pituitary which normally occurs on proestrus, prior to ovulation. Oestrous cyclicity was lost when diabetes was induced for 14 or 56 days, but there was no effect on pituitary responsiveness to luteinizing hormone-releasing hormone compared with control animals. Similar observations were made with rats placed on a food-restricted diet. In all experiments there was no difference between diabetic and control animals in the pituitary luteinizing hormone content, the hypothalamic content of luteinizing hormone-releasing hormone or the ovarian weights. Ovariectomized rats treated with streptozotocin (40 mg/kg) were used to investigate the effects of diabetes on steroid feedback mechanisms. There was an attenuated luteinizing hormone response to ovariectomy in diabetic compared with control animals, and an impaired positive feedback effect of progesterone in oestrogen-primed animals. The results show that streptozotoein-induced diabetes mellitus inhibits feedback action of gonadal steroids and this could account for both the loss of oestrous cyclicity and the reduced pituitary sensitivity to luteinizing hormone-releasing hormone.Key words: Streptozotocin, diabetes mellitus, fertility, luteinizing hormone, luteinizing hormone -releasing hormone, steroid feedback, body weight.It is well known that diabetic patients show an increased incidence of infertility [1], but the mechanisms by which diabetes mellitus impairs reproductive functions are poorly understood. Drug-induced diabetes mellitus in the female rat has frequently been used as an experimental model to investigate the causes of this association, since both alloxan-and streptozotocin-induced diabetes result in ovulatory failure [2,3]. A reduced sensitivity of the pituitary gonadotrophs to luteinizing hormone-releasing hormone (LHRH) has been observed in diabetic rats [4] but this could be attributed to an impairment of LHRH secretion since the releasing hormone regulates its own pituitary receptors [5]. Indeed, the available evidence strongly indicates that diabetes inhibits the hypothalamic regulation of gonadotrophin secretion, and this could involve a failure in the feedback action of gonadal steroids. However, a direct effect of diabetes on the pituitary gland or on the ovary cannot be excluded.The majority of studies have been carried out on the immature animal in which ovulation is stimulated by the administration of pregnant mare's serum gonadotrophin. This particular animal model has some disadvantages since it precludes the c...

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“…Considering both the impairments in the metabolic and steroidsupportive aspects of CNS function in the (db/db) mice, it is suspected that the gradual structural changes observed in the hypotha lamic nuclei that are recognized to modulate autonomic nervous system control of pitu itary, pancreatic and reproductive function are directly attributable to an imbalance of normal neuronal metabolism. Althogh glu cose is the primary energy substrate of the brain [49], the hyperglycemic condition asso ciated with the diabetic state has been dem onstrated to induce neuropathological changes [32][33][34], Ultimately, the neuronal degeneration associated with the prolonged hyperglycemic state may be induced by a metabolic imbalance in the neurons, which also renders them unresponsive to continued steroid modulation and/or support. The close association between glucose regulatory and steroid-concentrating neurons in the hypo thalamus [25, 26, 29.…”

Section: Discussionmentioning

confidence: 99%

“…30, 31, 44]. Recent studies have indicated that the ventromedial (VMH) and arcuate (ARC) nuclei in the medial basal hypotha lamic (MBH) zone undergo degenerative changes in association with progressive hy perglycemia [32][33][34]45]. Since these nuclear areas are well recognized to selectively se quester, and respond to, circulating E and P, it has been postulated that one of the compli cations of peripheral tissue dysfunction may result from the diabetes-induced, functional impairment of steroid-sensitive neurons in the MBH and related limbic system nuclei [6-8.…”

Section: Introductionmentioning

confidence: 99%

Depressed Progesterone Accumulation by the Brain and Peripheral Tissues of Diabetic C57BL/KsJ Mice: Normalization by Estrogen Therapy

Garris

1987

Horm Res

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The effects of diabetes on the uptake and incorporation of ³H-progesterone (P) in various brain areas and peripheral tissues were analyzed in C57BL/KsJ mice. Littermate control (+/?) and diabetic (db/db) mice were pulse-treated (60) min with 10 µCi of ³H-P at either 8 or 16 weeks of age. Subsequently, the peripheral tissues and brains were dissected, weighed, digested and the amount of incorporated ³H-P assessed. The pituitary, amygdala, septum and hypothalamus were found to concentrate the highest levels of ³H-P of all the brain areas examined. The brain areas of 16-week-old (+/?) mice accumulated higher concentrations of ³H-P than the comparable 8-week-old brain tissues. In addition, all the brain areas of 8-week-old (db/db) mice accumulated equal or more ³H-P than the comparable (+/?) brains. By 16 weeks of age, however, the ³H-P accumulation rate was significantly higher in all brain areas of (+/?), as compared to (db/db), mice. Of the peripheral tissues examined, the ovary, uterus, pancreas, kidney and mesometrial fat pad consistently exhibited the highest rates of ³H-P accumulation in both (+/?) and (db/db) mice. By 16 weeks of age, all peripheral tissues of (+/?) mice exhibited greater accumulation rates of ³H-P than the comparable (db/db) tissues. Following 4 days of estradiol treatment (10 µg/day s.c), the ³H-P accumulation rates in 16-week-old (+/?) and (db/db) brain were essentially equal. Only the hypothalamus, septum and amygdala of the (db/db) mice failed to normalize to (+/?) levels following estradiol treatment. In a similar manner, the pancreas, uterus, ovary and fat of (db/db) mice exhibited ³H-P accumulation rates similar to those of (+/?) mice following estradiol treatment. These data indicate that estradiol therapy effectively normalizes the normal age- and diabetes-related declines in brain and peripheral tissue sensitivity and/or responsitivity to progesterone in C57BL/KsJ mice.

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Morphometric evaluation of the hypothalamic-ovarian axis of the ketonuric, diabetic Chinese hamster: Relationship to the reproductive cycle

Cited by 43 publications

References 16 publications

Estrogenic Stimulation of Hypothalamic-Limbic System Metabolism in Ageing Diabetic C57BL/KsJ Mice

Estrogenic Stimulation of Hypothalamic-Limbic System Metabolism in Ageing Diabetic C57BL/KsJ Mice

Feedback effects of steroids and gonatrophin control in adult rats with streptozotocin-induced diabetes mellitus

Depressed Progesterone Accumulation by the Brain and Peripheral Tissues of Diabetic C57BL/KsJ Mice: Normalization by Estrogen Therapy

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