The Hypothalamic-Pituitary Axis in Genetically Obese (ob/ob) Mice: Response to Luteinizing Hormone-Releasing Hormone*

Swerdloff, Ronald S.; Peterson, Margaret; Vera, Arnoldo; Batt, R. A. L.; Heber, David; Bray, George A.

doi:10.1210/endo-103-2-542

Cited by 82 publications

(43 citation statements)

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“…Gonadotropin secretion is impaired and very sensitive to the negative feedback of gonadal steroids, much as in prepubertal animals (12). It has recently been shown that chronic treatment with leptin can induce recovery in the reproductive system in the ob͞ob mouse by promoting growth and function of the reproductive organs and fertility (13,14) by increasing secretion of gonadotropins (15).…”

mentioning

confidence: 99%

Role of leptin in hypothalamic–pituitary function

Kimura²,

Walczewska³

et al. 1997

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

667

439

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A defect in the structure of the obese gene is responsible for development of obesity in the ob͞ob mouse. The product of expression of the gene is the protein hormone leptin. Leptin causes weight loss in ob͞ob and normal mice, it is secreted by adipocytes, and it is an important controller of the size of fat stores by inhibiting appetite. The ob͞ob mouse is infertile and has a pattern of gonadotropin secretion similar to that of prepubertal animals. Consequently, we hypothesized that leptin might play a role in the control of gonadotropin secretion and initiated studies on its possible acute effects on hypothalamic-pituitary function. After a preincubation period, hemi-anterior pituitaries of adult male rats were incubated with leptin for 3 hr. Leptin produced a dose-related increase in follicle-stimulating hormone (FSH) and luteinizing hormone (LH) release, which reached peaks with 10 ؊9 and 10 ؊11 M leptin, respectively. Gonadotropin release decreased at higher concentrations of leptin to values indistinguishable from that of control pituitaries. On the other hand, prolactin secretion was greatly increased in a dose-related manner but only with leptin concentrations (10 ؊7 -10 ؊5 M). Incubation with leptin of median eminence-arcuate nuclear explants from the same animals produced significant increases in LH-releasing hormone (LHRH) release only at the lowest concentrations tested (10 ؊12 -10 ؊10 M). As the leptin concentration was increased, LHRH release decreased and was significantly less than control release at the highest concentration tested (10 ؊6 M). To determine if leptin can also release gonadotropins in vivo, ovariectomized females bearing implanted third ventricle cannulae were injected with 10 g of estradiol benzoate s.c., followed 72 hr later by microinjection into the third ventricle of leptin (0.6 nmol in 5 l) or an equal volume of diluent. There was a highly significant increase in plasma LH, which peaked 10-50 min after injection of leptin. Leptin had no effect on plasma FSH concentrations, and the diluent had no effect on either plasma FSH or LH. Thus, leptin at very low concentrations stimulated LHRH release from hypothalamic explants and FSH and LH release from anterior pituitaries of adult male rats in vitro and released LH, but not FSH, in vivo. The results indicate that leptin plays an important role in controlling gonadotropin secretion by stimulatory hypothalamic and pituitary actions.

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mentioning

confidence: 99%

Role of leptin in hypothalamic–pituitary function

Kimura²,

Walczewska³

et al. 1997

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

667

439

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“…GnRH secretion in the ob/ob mouse is absent (Swerdloff et al, 1978), with the diminished levels of LH and FSH assumed to be the cause of sterility (Runner, 1954). Indeed, a 2-week leptin treatment of ob/ob mice has been shown to increase the levels of LH and FSH in both sexes (Barash et al, 1996), and results in normalized body weight (Pelleymounter et al, 1998) and restored fertility (Mounzih et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Ontogeny of leptin and its receptor expression in mouse testis during the postnatal period

Herrid

O’Shea

McFarlane

2007

Molecular Reproduction Devel

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The mechanism by which leptin regulate male reproductive development during postnatal periods remain to be determined. Using immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR), we established that leptin is expressed in mouse testis with a cell-type and stagedependent manner during the postnatal period. In testes of 5-day-old mice, leptin expression was mainly restricted to gonocytes, whereas the immunostaining of leptin was confined to spermatogonia in 10-day-old testes. From Day 20 and onwards, stage-specific expression of leptin was evident in spermatocytes at stages VII-XII of the cycle in the seminiferous epithelium. RT-PCR showed that leptin and its receptor isoforms, Ob-Ra, Ob-Rb, and Ob-Re were all expressed in testes from 5-to 60-day-old mice. The mRNA for Ob-Ra and Ob-Re, but not Ob-Rb or leptin were identified in both immature (14-day-old) and adult (60-day-old) isolated Leydig cells. These results suggest that besides its primary actions at the hypothalamic-pituitary level, leptin has direct effects in the proliferation, differentiation of germ cells and the modulation of testicular steroidogenesis, using both autocrine and paracrine mechanisms. Mol.

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“…It may act also as an important regulator of neuroendocrine and reproductive functions. Leptin-deficient ob/ob mice exhibit infertility caused by hypothalamic dysfunction (13), which is corrected by exogenous administration of leptin (14,15). Short-term administration of leptin accelerates the onset of puberty in normal mice (16,17) and rescues the impaired reproductive homeostasis in fasted mice and rats with reduced amounts of leptin (18)(19)(20).…”

Section: Introductionmentioning

confidence: 99%