Correction of the sterility defect in homozygous obese female mice by treatment with the human recombinant leptin

Chehab, Farid F.; Lim, Mary E.; Lu, Ronghua

doi:10.1038/ng0396-318

Cited by 1,476Hypothalamic control of reproductive hormonesRegulation of Appetite and ObesityReproductive Biology and Fertility

Correction of the sterility defect in homozygous obese female mice by treatment with the human recombinant leptin

Chehab, Farid F., Lim, Mary E., Lu, Ronghua·1996·Nature Genetics

DOI 10.1038/ng0396-318

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Abstract

The sterility of male and female homozygous ob/ob mice is a recognized feature of the ob mutation (1). Whereas ob/ob males can occasionally reproduce if maintained on a restricted diet, ob/ob females are always sterile (2). Thinning of the ob/ob females to normal weight by diet-restriction failed to correct their sterility. Early sexual development is normal in ob/ob females; however, ovulation never follows and the mice remain prepuberal indefinitely with no occurrence of oestrus cycles. Reproductive hormones are reduced in ob/ob females (3) demonstrating a functional defect from the hypothalamic-pituitary axis (4-6). The ovaries of ob/ob females are capable of producing viable eggs when transplanted into lean female recipients (7). Reconstitution of reproductive functions in the ob/ob female necessitates delivery of hypothalamic extracts to the third ventricle (8) and administration of pituitary extract (9), gonadotropic hormones (10), progesterone (11) and relaxin (12). These previous findings demonstrate that the sterility of ob/ob females is caused by an insufficiency of hormones at the hypothalamic-pituitary level rather than physical hindrance of copulatory activity, pregnancy and parturition caused by excess adipose tissue. We show here that repeated administration of only the recombinant human ob protein, leptin, into homozygous female ob/ob mice can correct their sterility, thus resulting in ovulation, pregnancy and parturition.

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Exogenous leptin corrects the sterility of leptin-deficient ob/ob mice.
“and corrects the sterility of leptin-deficient ob/ob mice (29, 30).”
From The role of falling leptin levels in the neuroendocrine and metabolic adaptation to short-term starvation in healthy men (2003) · cites this paper as [29]

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Papathanasiou, A. E., Nolen-Doerr, E., Farr, O. M., & Mantzoros, C. S. (2019) · European Journal of Endocrinology · doi:10.1530/eje-18-0847 · Cited by 20 · see citing works

Authors: Chehab, F. F., Lim, M. E., & Lu, R.
Affiliations: University of California, San Francisco (US)
Venue: Nature Genetics
Publisher: Springer Science and Business Media LLC
Published: 1996-03
Volume: 12
Issue: 3
Pages: 318-320
ISSN: 1061-4036 (ISSN-L)
1546-1718
DOI: 10.1038/ng0396-318
OpenAlex: W2055956383
Cited by: 1,476
References: 17
Citations by year: 2026: 10 · 2025: 19 · 2024: 15 · 2023: 18 · 2022: 28 · 2021: 26 · 2020: 28 · 2019: 25 · 2018: 30 · 2017: 33 · 2016: 37 · 2015: 33 · 2014: 52 · 2013: 43 · 2012: 57
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature Genetics (publishedVersion)
PubMed (publishedVersion)
Funders: National Heart, Lung, and Blood Institute (HL53762, P01HL053762)
Topics: Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
Keywords: leptin, ob/ob mice, female infertility, reproductive sterility, ovulation, hypothalamic-pituitary axis, recombinant human leptin, pregnancy, childbirth, obesity, adipose tissue
MeSH terms: Animals, Base Sequence, Female, Homozygote, Humans, Infertility, Female, Male, Mice, Inbred C57BL, Mice, Obese, Molecular Sequence Data, Obesity, Pregnancy, Proteins, Recombinant Proteins, Polymerase Chain Reaction, DNA Primers, Leptin, Mice

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Correction of the sterility defect in homozygous obese female mice by treatment with the human recombinant leptin

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