Short term hypothyroidism affects ovarian function in the cycling rat

Hapon, María Belén; Gamarra-Luques, Carlos; Jahn, Graciela A.

doi:10.1186/1477-7827-8-14

Cited by 50 publications

(41 citation statements)

References 46 publications

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“…GH stimulates IGF-1 secretion in the liver and in the mammary stroma, therefore a paracrine role of GH modulating the effects of other hormones on proliferation and differentiation of mammary epithelium must not be ruled out (28). The present results demonstrated that hypothyroidism diminishes the secretion of GH in the rat, supporting previous studies (29).…”

Section: Discussionsupporting

confidence: 82%

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Experimental hypothyroidism increases apoptosis in dimethylbenzanthracene-induced mammary tumors

et al. 2013

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Abstract. Epidemiological and in vitro data have not provided conclusive evidence concerning the involvement of thyroid hormones (THs) on mammary carcinogenesis. We used an in vivo model to assess the relationship between THs, adipose tissue and breast cancer development. Female Sprague-Dawley rats were treated with a dose of 7,12-dimethylbenz(a)anthracene (15 mg/rat) at 55 days of age and were then divided into four experimental groups: hypothyroid rats (HypoT, 0.01% 6-N-propyl-2-thiouracil in drinking water), untreated control (EUT); hyperthyroid rats (HyperT, 0.25 mg/kg/day T 4 s.c.) and vehicle-treated control rats. The latency of tumor appearance and the incidence and progression of tumors were determined. At sacrifice, blood samples were collected for hormone determinations and samples of tumor and mammary glands were obtained for immunohistological studies. HypoT rats had retarded growth and an increase in mammary fat. The latency was longer (p<0.0001), the incidence rate was lower (p<0.05) and tumor growth was slower in HypoT rats compared to EUT and HyperT rats. Mitotic index and PCNA immunostaining were similar in all groups. HypoT rats showed increased apoptosis (p<0.05) as evaluated by the apoptotic index and TUNEL staining. No differences in serum prolactin and progesterone were observed. However, circulating estradiol (E 2 ) was significantly lower in HypoT and HyperT rats. Serum leptin levels were reduced in HypoT rats even though the abdominal fat mass was similar in all groups. To note, the leptin level was higher in HypoT rats that developed mammary tumors than the level in non-tumoral HypoT rats. In conclusion, hypothyroidism altered animal growth, breast morphology, body composition, leptin secretion and serum E 2 enhancing apoptosis and, consequently, retarding mammary carcinogenesis in rats.

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Section: Discussionsupporting

confidence: 82%

“…It has been previously shown that hypothyroidism can increase serum levels of PRL during estrous without changing basal secretion on diestrous day (29). In the present study, based on the similar values of circulating PRL between the treatments, we cannot attribute a relevant role of this hormone on mammary carcinogenesis.…”

Section: Discussioncontrasting

confidence: 41%

Experimental hypothyroidism increases apoptosis in dimethylbenzanthracene-induced mammary tumors

et al. 2013

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“…For example, lower Igf-I levels are found in rodents that are hypothyroid and in females that do not go through proestrus (70), and both chronic HPA axis activation and circadian disruption are associated with obesity (71,72). We did note a marked overlap between the endocrine profile of Magel2-null mice and that of rodents with congenital leptin resistance, in contrast to rodents with diet-induced obesity.…”

Section: Endocrine Phenotypes Of Magel2-null Mice Resemble Those Founmentioning

confidence: 73%

Impaired Hypothalamic Regulation of Endocrine Function and Delayed Counterregulatory Response to Hypoglycemia in Magel2-Null Mice

Tennese

Wevrick

2011

Endocrinology

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Hypothalamic dysfunction may underlie endocrine abnormalities in Prader-Willi syndrome (PWS), a genetic disorder that features GH deficiency, obesity, and infertility. One of the genes typically inactivated in PWS, MAGEL2, is highly expressed in the hypothalamus. Mice deficient for Magel2 are obese with increased fat mass and decreased lean mass and have blunted circadian rhythm. Here, we demonstrate that Magel2-null mice have abnormalities of hypothalamic endocrine axes that recapitulate phenotypes in PWS. Magel2-null mice had elevated basal corticosterone levels, and although male Magel2-null mice had an intact corticosterone response to restraint and to insulin-induced hypoglycemia, female Magel2-null mice failed to respond to hypoglycemia with increased corticosterone. After insulin-induced hypoglycemia, Magel2-null mice of both sexes became more profoundly hypoglycemic, and female mice were slower to recover euglycemia, suggesting an impaired hypothalamic counterregulatory response. GH insufficiency can produce abnormal body composition, such as that seen in PWS and in Magel2-null mice. Male Magel2-null mice had Igf-I levels similar to control littermates. Female Magel2-null mice had low Igf-I levels and reduced GH release in response to stimulation with ghrelin. Female Magel2-null mice did respond to GHRH, suggesting that their GH deficiency has a hypothalamic rather than pituitary origin. Female Magel2-null mice also had higher serum adiponectin than expected, considering their increased fat mass, and thyroid (T 4 ) levels were low. Together, these findings strongly suggest that loss of MAGEL2 contributes to endocrine dysfunction of hypothalamic origin in individuals with PWS. (Endocrinology 152: 967-978, 2011) P rader-Willi syndrome (PWS) is a complex genetic disorder, whose clinical features suggest abnormalities of the hypothalamic-pituitary axis. These include GH deficiency with short stature, increased fat mass and reduced lean mass, hypogonadotropic hypogonadism, childhood-onset hyperphagia and obesity, and sleep disorders. Structural abnormalities of the brain documented in PWS include frequent ventriculomegaly and cortical abnormalities. Pituitary abnormalities are common, but structural abnormalities of the hypothalamus are not typically found (1-3). Children with PWS typically have decreased spontaneous GH secretion and low peak GH response in stimulation tests (4, 5), accompanied by reduced serum IGF-I and low IGF-binding protein 3 (6 -8). GH deficiency contributes to abnormal body composition consisting of increased body fat mass and reduced lean mass, and treatment with GH partially normalizes body composition and short stature (9 -11). In contrast, obesity in the general population is often associated with a relative GH deficiency but normal or high levels of IGF-I, suggesting defective feedback mechanisms in GH pathways that can resolve on weight loss.In normal adults, serum leptin levels increase with increasing adiposity, but levels of adiponectin, particularly in its multimeric high mole...

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“…The presence of these receptors in the uterus could be related to the implantation process. Hyper or hypothyroidism affect the implantation sites, the incidence of resorptions (7)(8), the oxidative status in the uterus (9), and the leucocyte infiltration into the endometrial stroma (4) in rats. Additionally, hypothyroidism reduces the weight of the uterus in rats (40) as well as the number and force of the uterine contractions in bitches (11) and rats (5)(6).…”

Section: Discussionmentioning

confidence: 99%

“…Both hyperthyroidism and hypothyroidism have been associated with menstrual disturbances, miscarriages, and infertility in women (1)(2). Hyper or hypothyroid rats show modifications in the angiogenesis and proliferation of luteal cells of the corpus luteum (3), the amount of carbohydrates in the ovaries and endometrium (4), the oviductal and uterine contractility (5)(6), the implantation sites and the incidence of resorptions (7)(8), and the oxidative status of the uterus (9). Hypothyroidism increases the size of oviductal epithelial cells in rabbits (10).…”

Section: Introductionmentioning

confidence: 99%

Distribution of thyroid hormone and thyrotropin receptors in reproductive tissues of adult female rabbits

et al. 2016

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Short term hypothyroidism affects ovarian function in the cycling rat

Cited by 50 publications

References 46 publications

Experimental hypothyroidism increases apoptosis in dimethylbenzanthracene-induced mammary tumors

Experimental hypothyroidism increases apoptosis in dimethylbenzanthracene-induced mammary tumors

Impaired Hypothalamic Regulation of Endocrine Function and Delayed Counterregulatory Response to Hypoglycemia in Magel2-Null Mice

Distribution of thyroid hormone and thyrotropin receptors in reproductive tissues of adult female rabbits

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