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-Rhinehart, Erin; Kalra, Satya P.; Kalra, Pushpa S.

doi:10.1095/biolreprod.103.025858

Cited by 17 publications

(9 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Conversely, treatment with exogenous leptin can restore some measure of fertility to animals lacking leptin (33), but not those with dysfunctional ObR (70). However, introduction of ObR into the brains of ObR-deficient Zucker rats with a viral vector restores estrous cyclicity (123). At the very least, these findings indicate that some level of leptin signaling is required for fertility.…”

Section: Peripheral Detectors With Humoral Transmission To the Cnsmentioning

confidence: 99%

Neuroendocrinology of nutritional infertility

Wade¹,

Jones²

2004

American Journal of Physiology-Regulatory, Integrative and Comp

229

166

View full text Add to dashboard Cite

Natural selection has linked the physiological controls of energy balance and fertility such that reproduction is deferred during lean times, particularly in female mammals. In this way, an energetically costly process is confined to periods when sufficient food is available to support pregnancy and lactation. Even in the face of abundance, nutritional infertility ensues if energy intake fails to keep pace with expenditure. A working hypothesis is proposed in which any activity or condition that limits the availability of oxidizable fuels (e.g., undereating, excessive energy expenditure, diabetes mellitus) can inhibit both gonadotropin-releasing hormone (GnRH)/luteinizing hormone secretion and female copulatory behaviors. Decreases in metabolic fuel availability appear to be detected by cells in the caudal hindbrain. Hindbrain neurons producing neuropeptide Y (NPY) and catecholamines (CA) then project to the forebrain where they contact GnRH neurons both directly and also indirectly via corticotropin-releasing hormone (CRH) neurons to inhibit GnRH secretion. In the case of estrous behavior, the best available evidence suggests that the inhibitory NPY/CA system acts primarily via CRH or urocortin projections to various forebrain loci that control sexual receptivity. Disruption of these signaling processes allows normal reproduction to proceed in the face of energetic deficits, indicating that the circuitry responds to energy deficits and that no signal is necessary to indicate that there is an adequate energy supply. While there is a large body of evidence to support this hypothesis, the data do not exclude nutritional inhibition of reproduction by other pathways and processes, and the full story will undoubtedly be more complex than this. luteinizing hormone; estrous behavior; corticotropin-releasing hormone; neuropeptide Y; hindbrain OF NECESSITY, the physiological controls of reproduction and energy balance are closely intertwined. Living creatures require a steady stream of oxidizable substrates to fuel their many energy-consuming activities, including reproduction. But in nature, energetic demands and opportunities for meal taking can be erratic and sometimes unpredictable, necessitating the existence of physiological and behavioral strategies to maximize chances of individual survival and permit propagation of the species (21,22,200,208).A need to eat constantly is obviated by the presence of internal caloric buffers that store glycogen and fatty acids and provide sustenance in between meals and during brief fasts. When food is abundant, animals adjust their intakes to meet all demands and keep their storage depots full (or overfull in an increasing number of cases). However, a more likely scenario in nature and during human evolution is that food can be scarce or have a very high acquisition cost. In that case, animals adjust their energetic priorities, i.e., how they partition and use the available metabolic fuels (Fig.

show abstract

Section: Peripheral Detectors With Humoral Transmission To the Cnsmentioning

confidence: 99%

Neuroendocrinology of nutritional infertility

Wade¹,

Jones²

2004

American Journal of Physiology-Regulatory, Integrative and Comp

229

166

View full text Add to dashboard Cite

show abstract

“…Its receptor (leptin receptor, LEPR) has been localized to several hypothalamic nuclei, including the ventromedial hypothalamus, the medial preoptic area, the paraventricular nucleus, and the arcuate nucleus (Keen-Rhinehart et al 2004). LEPR belongs to the class I cytokine receptor superfamily that shares common structural features and signal transduction pathways (Tartaglia et al 1995).…”

Section: Introductionmentioning

confidence: 99%

Novel SNPs of the Bovine LEPR Gene and Their Association with Growth Traits

et al. 2008

View full text Add to dashboard Cite

In this study, polymorphism in the bovine LEPR gene exon 4 was detected by PCR-SSCP and DNA sequencing methods in 653 individuals from five Chinese cattle breeds. Two haplotypes (M and N), three observed genotypes (MM, MN, and NN), and five single nucleotide polymorphisms (SNPs) (NC_007301:g.26767T>C, NC_007301:g.26805C>T, NC_007301:g.27050A>G, NC_007301:g.27063G>A, NC_007301:g.27079G>A) were detected. The frequencies of haplotypes M and N in the five breeds were 0.661-0.747 and 0.253-0.339, respectively. The SNP locus was in Hardy-Weinberg equilibrium in Nanyang, Jiaxian red, Angus, and Jinnan cattle (P > 0.05) and was in Hardy-Weinberg disequilibrium in Qinchuan cattle (P < 0.05). Polymorphism of the LEPR gene was shown to be associated with growth traits in the Nanyang breed. The SNP in the bovine LEPR gene had significant effects on body height, body length, body weight, heart girth, and average daily gain at 6 and 12 months old (P < 0.01 or P < 0.05). Therefore, these results suggest that the LEPR gene is a strong candidate gene that affects growth traits in cattle.

show abstract

“…In addition to a pivotal role in hypothalamic integration of energy homeostasis, the hypothalamic NPY network has since been shown to play a role in neuroendocrine control of reproduction and lactation, fluid balance, growth, stress, temperature, general body metabolism and bone health (1,12,15,31,41,45,46,48,62). It is now obvious that disruption in any one or more loci in the hypothalamic network of NPY and cohorts inflicted by environmental or genetic factors leads to several metabolic and neuroendocrine diseases that adversely affect the quality of life and life span (1,4,(24)(25)(26)30,32,47).…”

Section: Introductionmentioning

confidence: 99%

To subjugate NPY is to improve the quality of life and live longer

Kalra

2007

Peptides

Self Cite

View full text Add to dashboard Cite

The interactive network of Neuropeptide Y (NPY) and cohorts is necessary for integrating the hypothalamic regulation of appetite and energy expenditure with the endocrine and neuroendocrine systems on a daily basis. Genetic and environmental factors that produce an insufficiency of leptin restraint on NPY and cognate receptors deregulate the homeostasis to engender various lifethreatening risk factors. Recent studies from our laboratory show that neurotherapy consisting of a single central administration of recombinant adeno-associated virus vector encoding the leptin gene can repress the hypothalamic NPY system for the lifetime of rodents. A major benefit of this stable tonic restraint is deceleration of pathophysiologic sequalae that shorten life span. These include suppression of weight gain, fat accumulation, circulating adipokines, amelioration of major symptoms of metabolic syndrome, improved reproduction and bone health. Thus, sustained repression of NPY signaling in the hypothalamus by leptin transgene expression can improve the quality of life and extend longevity.

show abstract

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

Cited by 17 publications

References 71 publications

Neuroendocrinology of nutritional infertility

Neuroendocrinology of nutritional infertility

Novel SNPs of the Bovine LEPR Gene and Their Association with Growth Traits

To subjugate NPY is to improve the quality of life and live longer

Contact Info

Product

Resources

About