Cyclical Variations in the Abundance of Leptin Receptors, but not in Circulating Leptin, Correlate with NPY Expression during the Oestrous Cycle

Bennett, Pamela A.; Lindell, Kajsa; Wilson, Carole L.; Carlsson, Lena; Carlsson, Björn; Robinson, Iain C. A. F.

doi:10.1159/000054444

Cited by 67 publications

(56 citation statements)

References 44 publications

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“…These results, together with those obtained in this work, suggest that oestrogens could be exerting a negative feedback on the expression of leptin receptors in the hypothalamic tissue. These data support the results obtained by Bennett et al (1998Bennett et al ( , 1999 who demonstrated that oestrogens modulate the expression of the hypothalamic leptin receptors. On the other hand, it is likely that the expression of leptin receptors in the peripheral tissues is also modulated by steroids, since a positive relationship between steroids and leptin receptors in both the pituitary and ovarian tissue seems to exist.…”

Section: Ctrlsupporting

confidence: 92%

Leptin modulates the expression of its receptors in the hypothalamic–pituitary–ovarian axis in a differential way

Yorio¹,

Bilbao²,

Pustovrh³

et al. 2008

Journal of Endocrinology

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To investigate the expression of leptin receptors (Ob-R) in the rat hypothalamus-pituitary-ovarian axis, immature rats were treated with eCG/hCG and Ob-R expression was evaluated by western blot analysis. The Ob-R expression increased 24 h after eCG administration in all the tissues assayed. In the hypothalamus, these levels immediately decreased to those obtained without treatment. In the pituitary, the Ob-R expression continued to be elevated 48 h after eCG administration, whereas the hCG injection did not modify these levels. Similar results were obtained with the ovarian long isoform. To assess the effect of leptin on its receptors, Ob-R was assessed in hypothalamus, pituitary and ovarian explants cultured in the presence or absence of leptin (0 . 3-500 ng/ml). In the hypothalamus, we found a biphasic effect: the Ob-R expression was either reduced or increased at low or high concentrations of leptin respectively. LH-releasing hormone secretion increased at 1 ng/ml. In the pituitary, Ob-R increased at 10 or 30 ng/ml of leptin for the long and short isoforms respectively. Leptin also induced an increase in LH release at 30 ng/ml. In the ovarian culture, the presence of leptin produced an increase in Ob-R expression at different ranges of concentrations and a dosedependent biphasic effect on the progesterone production. In conclusion, all these results clearly suggest that leptin is able to modulate the expression of its own receptors in the reproductive axis in a differential way. Moreover, the positive or negative effect that leptin exerts on the ovulatory process may be dependent on this regulation.

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Section: Ctrlsupporting

confidence: 92%

Leptin modulates the expression of its receptors in the hypothalamic–pituitary–ovarian axis in a differential way

Yorio¹,

Bilbao²,

Pustovrh³

et al. 2008

Journal of Endocrinology

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“…This ovarian modulation of feeding involves a phasic, or cycling, inhibition that is mediated by decreased food intake during estrus in intact rats [19]. We and others have previously shown that there are no significant variations in circulating leptin levels during the estrous cycle in rats [17,30]. This is concordant with the results in this study, where no changes were seen between day 2 (proestrus) and day 3 (estrus).…”

Section: Discussionsupporting

confidence: 92%

“…Furthermore, estradiol levels vary throughout the cycle with peak levels in pro-estrus and lower levels during the other stages [17,22]. A reduction in food intake, preceded…”

Section: Discussionmentioning

confidence: 99%

“…The cause of leptin resistance is still the cause of considerable debate, however numerous studies provide support for a role of an inhibitory molecule called suppressor of cytokine signalling-3 (SOCS3) in the regulation of leptin receptor signaling, both in vivo and in vitro [14,15]. It is also possible that regulation of leptin receptor abundance can affect leptin response, and we have previously shown that mRNA levels of leptin receptors are highly regulated in response to estrogen, fasting, ovariectomy and during a spontaneous estrous cycle [16,17]. In humans, energy intake is higher in the postovulatory or premenstrual phase of the cycle than in the preovulatory or follicular phase [18]; and it has long been known that the food intake and body weight of rats fluctuate during the estrous cycle [19].…”

Section: Introductionmentioning

confidence: 99%

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Hypothalamic response to leptin changes during a hormonally induced estrous cycle in rats

Sjöholm

Carlsson

2006

Open Life Sciences

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Abstract:The leptin system regulates body fat mass through a feedback loop between adipose tissue and the hypothalamus. To test if leptin responsiveness may be regulated we assayed hypothalamic response to leptin during the estrous cycle; when changes in food intake are known to occur. Immature rats were treated with pregnant mare's serum gonadotropin (PMSG) to induce synchronized follicular development, ovulation and corpus luteum formation. Leptin response was estimated by measuring the in vitro induction of tis11, a primary response gene activated by STAT3-dependent cytokines in hypothalamic explants after leptin stimulation. In addition, mRNA levels of the suppressor cytokine signaling-3 (SOCS-3), a possible mediator of leptin resistance, were analyzed. Serum leptin levels did not change between days 2 and day 3 (corresponding to proestrus and estrus, respectively) but the response to leptin was higher on day 2 than on day 3 (p=0.05). Food intake displayed a tendency towards downregulation between day 1 and day 2 (p=0.057), and a tendency towards upregulation between day 2 and day 3 (p=0.072), although the body weight increased on day of the study (p<0.0001). There was no significant difference in hypothalamic expression of SOCS-3 between day 2 and day 3. In conclusion, we have shown that leptin responsiveness changes during a hormonally induced estrous cycle in rats. Our data suggest that a change in the hypothalamic response to leptin may cause the cyclic feeding behavior seen in rats.

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“…Several neurotransmitters and receptors exhibiting sexual dimorphisms in ARC and its surroundings, such as noradrenalin, galanin, NPY, neurotensin, ␤-endorphin, glutamate, proopiomelanocortin, and leptin receptors have been reported to show estrous cycle-related changes (14,(25)(26)(27)(28)(29). These molecules have been thought to contribute to energy homeostasis and reproductive functions.…”

Section: Discussionmentioning

confidence: 99%

A recently identified hypothalamic nucleus expressing estrogen receptor α

Mori¹,

Matsuda²,

Pfaff³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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We report evidence for the existence of a unique nucleus in the rat hypothalamus. This nerve cell group is situated in the interstitial area between the arcuate nucleus and ventromedial nucleus of the hypothalamus, and is primarily oriented sagittally, in a spindle shape. This nucleus was a well defined structure in Nissl-stained sections because of its location in an otherwise cell-poor zone. This sagittalis nucleus of the hypothalamus (SGN) exhibits significant sex differences in its volume and cell numbers, as defined by Nissl staining and estrogen receptor (ER) ␣ immunoreactivity (ir), being significantly larger in males than in females. Treatment of neonatal females with testosterone eliminated these sex differences. It is noteworthy that adult female rats have estrous cycle-related variations in the ER␣-ir cell distribution, decreasing during the proestrus phase of the cycle. Pharmacological experiments demonstrated that the single injection of estradiol benzoate had a significant effect on the ER␣-ir cell count, suggesting the hormonal responsiveness of SGN neurons. This unique hypothalamic nucleus with its morphological sex differences and hormonal responsiveness is embedded in a region important for the regulation of endocrine functions and sexual behaviors.sexual difference ͉ estrous cycle ͉ calbindinD-28k ͉ sagittalis nucleus A fter the comprehensive neuroanatomical charting of neurons expressing mRNAs for estrogen receptors (1) and subsequent estradiol binding (2), it was assumed that the understanding of the neuroanatomy of estrogen action in the brain was fairly complete. Here, however, we have discerned a hitherto unrecognized cell group that expresses estrogen receptor (ER) ␣ and exhibits sex differences.A number of important sex differences have already been described in the mammalian brain (3, 4). Most of these are organized by the action of the gonadal steroids in the critical period: during the few days before to after birth in rodents (4). In this period, an elevated amount of testosterone (T) is secreted from the male fetal testes and converted to estradiol (E) by the enzyme aromatase in the hypothalamus. Formation of E causes permanent masculinization of the brain (5). This masculinization is also experimentally induced in females by the administration of E in the critical period (3, 6). These morphological sex differences in the brain are likely among the neuroanatomical mechanisms for the physiological sex differences in adult brain function (7,8).At the age of puberty, the functional sex-related differences begin to appear, indicated by a sudden rise in the secretion of gonadotrophic hormones: luteinizing hormone (LH) and follicle-stimulating hormone, followed by an increase in gonadal steroids (9). The gonadal steroids, particularly E, orchestrate the neuroendocrine circuits that coordinate sex-specific behaviors. This E signaling is importantly mediated by ERs (3), which are in fact abundant in the sexual dimorphic nuclei in the hypothalamus, such as the anteroventral periventricular ...

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Cyclical Variations in the Abundance of Leptin Receptors, but not in Circulating Leptin, Correlate with NPY Expression during the Oestrous Cycle

Cited by 67 publications

References 44 publications

Leptin modulates the expression of its receptors in the hypothalamic–pituitary–ovarian axis in a differential way

Leptin modulates the expression of its receptors in the hypothalamic–pituitary–ovarian axis in a differential way

Hypothalamic response to leptin changes during a hormonally induced estrous cycle in rats

A recently identified hypothalamic nucleus expressing estrogen receptor α

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