Circulating reproductive hormones and hypothalamic oestradiol and progestin receptors in infertile Zucker rats

Whitaker, E. M.; Robinson, A.

doi:10.1677/joe.0.1200331

Cited by 8 publications

(5 citation statements)

References 21 publications

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“…In the female fatty Zucker rats lacking a functional OB-R, estrous cycles are irregular, with long periods of diestrus [19,20]. The presence of several corpora lutea in the ovaries verified this observation.…”

Section: Discussionsupporting

confidence: 53%

“…The homozygous (fa/fa) fatty Zucker rat has a mutated OB-R gene that causes several perturbations in the hypothalamo-pituitary-gonadal (HPG) axis [16]. These rats are infertile, with abnormal estrous cycles, decreased plasma sex steroids, hyporesponsiveness to sexsteroid hormones, and attenuated sexual behavior and LH surge [14,[17][18][19][20].…”

Section: Introductionmentioning

confidence: 99%

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Leptin-Receptor Gene Transfer into the Arcuate Nucleus of Female Fatty Zucker Rats Using Recombinant Adeno-Associated Viral Vectors Stimulates the Hypothalamo-Pituitary-Gonadal Axis1

Keen-Rhinehart¹,

Kalra²,

Kalra³

2004

Biology of Reproduction

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Fatty fa/fa Zucker rats with a missense mutation in the leptin receptor (OB-R) are obese and infertile with prolonged estrous cycles. To determine whether their reproductive deficits could be corrected by OB-R installation, we employed viral vectors to introduce the OB-R gene into either the arcuate nucleus (ARC) or the paraventricular nucleus (PVN) of the hypothalamus, sites of OB-R expression in wild-type rats. Recombinant adeno-associated viral (rAAV) vectors encoding the human leptin-receptor gene (rAAV-OB-Rb) were microinjected intraparenchymally to produce doxycycline-regulatable OB-R gene expression. Expression of the OB-R gene in the ARC and PVN was verified using reverse transcription-polymerase chain reaction. Expression of OB-R in the ARC, but not in the PVN, resulted in normalization of estrous cycle length, increased ovarian follicular development, and decreased serum progesterone levels. Compared to saline-injected rats, hypothalamic expression of neuropeptide Y (NPY) and pro-opiomelanocortin were decreased in ARC rAAV-OB-Rb-injected rats. Parallel decreases were noted in NPY and beta-endorphin (beta-END) concentrations in the hypothalamus, whereas luteinizing hormone-releasing hormone (LHRH) levels increased. These studies showed that rAAV vectors can be successfully used to install functional OB-R in the hypothalamus for extended periods. The resultant stimulation of the hypothalamo-pituitary-gonadal (HPG) axis in ARC-injected rats was probably brought about by the observed decreases in NPY and beta-END, which inhibit hypothalamic LHRH. Because these changes were seen in ARC-injected, but not in PVN-injected, rats, the results suggest that the ARC may be the primary site where leptin acts to regulate the HPG axis.

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Section: Discussionsupporting

confidence: 53%

Section: Introductionmentioning

confidence: 99%

Leptin-Receptor Gene Transfer into the Arcuate Nucleus of Female Fatty Zucker Rats Using Recombinant Adeno-Associated Viral Vectors Stimulates the Hypothalamo-Pituitary-Gonadal Axis1

Keen-Rhinehart¹,

Kalra²,

Kalra³

2004

Biology of Reproduction

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“…Above data agree to our hormonal data about FSH, LH and estradiol in diestrous. In addition, they reported progesterone and prolactin concentrations were higher during most of the estrous cycle in fatty rats [32]. Unfortunately, we did not investigate hormonal data at each estrous cycle in this study.…”

Section: Discussionmentioning

confidence: 89%

“…They reported about plasma estradiol concentration and mentioned that the pattern of estradiol over the estrous cycle was similar in both rats and small difference was found in diestrous, although they did not analyze the statistical significance between fatty and lean rats [31]. In another study they also reported serum FSH, LH, progesterone and prolactin concentrations in fatty rats; proestrous peak concentration of LH was reduced and that of FSH was similar [32]. Above data agree to our hormonal data about FSH, LH and estradiol in diestrous.…”

Section: Discussionmentioning

confidence: 99%

Remarkable features of ovarian morphology and reproductive hormones in insulin-resistant Zucker fatty (fa/fa) rats

Honnma

Endo

Kiya

et al. 2010

Reprod Biol Endocrinol

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BackgroundZucker fatty (fa/fa) rats are a well-understood model of obesity and hyperinsulinemia. It is now thought that obesity/hyperinsulinemia is an important cause of endocrinological abnormality, but to date there have been no reports on the changes in ovarian morphology or the ovarian androgen profile in rat models of obesity and insulin resistance.MethodsIn this study we investigated the effects of obesity and hyperinsulinemia on ovarian morphology and the hormone profile in insulin-resistant Zucker fatty rats (5, 8, 12 and 16 weeks of age, n = 6-7).ResultsOvaries from 5-week-old fatty rats had significantly greater total and atretic follicle numbers, and higher atretic-to-total follicle ratios than those from lean rats. Ovaries from 12- and 16-week-old fatty rats showed interstitial cell hyperplasia and numerous cysts with features of advanced follicular atresia. In addition, serum testosterone and androstenedione levels significantly declined in fatty rats from age 8 to 16 weeks, so that fatty rats showed significantly lower levels of serum testosterone (12 and 16 weeks) and androstenedione (all weeks) than lean rats. This may reflect a reduction of androgen synthesis during follicular atresia. Serum adiponectin levels were high in immature fatty rats, and although the levels declined significantly as they matured, it remained significantly higher in fatty rats than in lean rats. On the other hand, levels of ovarian adiponectin and its receptors were significantly lower in mature fatty rats than in lean mature rats or immature fatty rats.ConclusionsOur findings indicate that ovarian morphology and hormone profiles are significantly altered by the continuous insulin resistance in Zucker fatty rats. Simultaneously, abrupt reductions in serum and ovarian adiponectin also likely contribute to the infertility seen in fatty rats.

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“…Sex hormones are also affected in both genders. Serum luteinizing hormone, folliclestimulating hormone, prolactin and progesterone fluctuation is impaired in female fa/fa rats, thus affecting fertility 130,131 . Additional endocrine disorders, such as hypothyroidism and GH/insulin-like growth factor-1 (GH/IGF-1) axis disruption, are observed in all ZFR 41,89,132 .…”

Section: Rat Models Of Monogenic Obesitymentioning

confidence: 99%

Rodent models of obesity

et al. 2020

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Obese or overweight people exceed one-third of the global population and obesity along with diabetes mellitus consist basic components of metabolic syndrome, both of which are known cardiocerebrovascular risk factors with detrimental consequences. These data signify the pandemic character of obesity and the necessity for effective treatments. Substantial advances have been accomplished in preclinical research of obesity by using animal models, which mimic the human disease. In particular, rodent models have been widely used for many decades with success for the elucidation of the pathophysiology of obesity, since they share physiological and genetic components with humans and appear advantageous in their husbandry. The most representative rodents include the laboratory mouse and rat. Within this review, we attempted to consolidate the most widely used mice and rat models of obesity and highlight their strengths as well as weaknesses in a critical way. Our aim was to bridge the gap between laboratory facilities and patient's bed and help the researcher find the appropriate animal model for his/her obesity research. This tactful selection of the appropriate model of obesity may offer more translational the derived results.. In this regard, we included, the main diet induced models, the chemical/mechanical ones as well as a selection of monogenic or polygenic models.

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Circulating reproductive hormones and hypothalamic oestradiol and progestin receptors in infertile Zucker rats

Cited by 8 publications

References 21 publications

Leptin-Receptor Gene Transfer into the Arcuate Nucleus of Female Fatty Zucker Rats Using Recombinant Adeno-Associated Viral Vectors Stimulates the Hypothalamo-Pituitary-Gonadal Axis1

Leptin-Receptor Gene Transfer into the Arcuate Nucleus of Female Fatty Zucker Rats Using Recombinant Adeno-Associated Viral Vectors Stimulates the Hypothalamo-Pituitary-Gonadal Axis1

Remarkable features of ovarian morphology and reproductive hormones in insulin-resistant Zucker fatty (fa/fa) rats

Rodent models of obesity

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