Roles of the lactogens and somatogens in perinatal and postnatal metabolism and growth: Studies of a novel mouse model combining lactogen resistance and growth hormone deficiency

Donald Fleenor, Jon Oden, Paul A. Kelly, Subburaman Mohan, Samira Alliouachene, Mario Pende, Sabrina Wentz, Jennifer Kerr, Michael Freemark

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

To delineate the roles of the lactogens and GH in the control of perinatal and postnatal growth, fat deposition, insulin production, and insulin action, we generated a novel mouse model that combines resistance to all lactogenic hormones with a severe deficiency of pituitary GH. The model was created by breeding PRL receptor (PRLR)-deficient (knockout) males with GH-deficient (little) females. In contrast to mice with isolated GH or PRLR deficiencies, double-mutant (lactogen-resistani and GH-deficient) mice on d 7 of life had growth failure and hypoglycemia. These findings suggest that lactogens and GH act in concert to facilitate weight gain and glucose homeostasis during the perinatal period. Plasma insulin and IGF-I and IGF-II concentrations were decreased in both GH-deficient and double-mutant neonates but were normal in PRLR-deficient mice. Body weights of the double mutants were reduced markedly during the first 3-4 months of age, and adults had striking reductions in femur length, plasma IGF-I and IGF binding protein-3 concentrations, and femoral bone mineral density. By age 6-12 months, however, the double-mutant mice developed obesity, hyperleptinemia, fasting hyperglycemia, relative hypoinsulinemia, insulin resistance, and glucose intolerance; males were affected to a greater degree than females. The combination of perinatal growth failure and late-onset obesity and insulin resistance suggests that the lactogen-resistant/GH-deficient mouse may serve as a model for the development of the metabolic syndrome.

Original languageEnglish (US)
Pages (from-to)103-112
Number of pages10
JournalEndocrinology
Volume146
Issue number1
DOIs
StatePublished - Jan 2005

Fingerprint

Growth Hormone
Prolactin Receptors
Growth
Insulin
Insulin-Like Growth Factor I
Insulin Resistance
Obesity
Insulin-Like Growth Factor Binding Protein 3
Insulin-Like Growth Factor II
Glucose Intolerance
Thigh
Hypoglycemia
Hyperglycemia
Bone Density
Femur
Weight Gain
Breeding
Fasting
Homeostasis
Fats

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Roles of the lactogens and somatogens in perinatal and postnatal metabolism and growth : Studies of a novel mouse model combining lactogen resistance and growth hormone deficiency. / Fleenor, Donald; Oden, Jon; Kelly, Paul A.; Mohan, Subburaman; Alliouachene, Samira; Pende, Mario; Wentz, Sabrina; Kerr, Jennifer; Freemark, Michael.

In: Endocrinology, Vol. 146, No. 1, 01.2005, p. 103-112.

Research output: Contribution to journalArticle

Fleenor, Donald ; Oden, Jon ; Kelly, Paul A. ; Mohan, Subburaman ; Alliouachene, Samira ; Pende, Mario ; Wentz, Sabrina ; Kerr, Jennifer ; Freemark, Michael. / Roles of the lactogens and somatogens in perinatal and postnatal metabolism and growth : Studies of a novel mouse model combining lactogen resistance and growth hormone deficiency. In: Endocrinology. 2005 ; Vol. 146, No. 1. pp. 103-112.
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