Paul A. Kelly

Body Weight and Fat Deposition in Prolactin Receptor-Deficient Mice1

To explore the roles of the lactogens in adipose tissue development and function, we measured body weight, abdominal fat content, and plasma leptin concentrations in a unique model of lactogen resistance: the PRL receptor (PRLR)-deficient mouse. The absence of PRLRs in knockout mice was accompanied by a small (5-12%), but progressive, reduction in body weight after 16 weeks of age. Females were affected to a greater degree than males. The reduction in weight in female PRLR-deficient mice (age 8-9 months) was associated with a 49% reduction in total abdominal fat mass and a 29% reduction in fat mass expressed as a percentage of body weight. Lesser reductions were noted in male mice. Plasma leptin concentrations were reduced in females but not in males. That the reductions in abdominal fat may reflect in part the absence of lactogen action in the adipocyte is suggested by the demonstration of PRLR messenger RNA in normal mouse white adipose tissue. Nevertheless, steady state levels of PRLR messenger RNA in mature adipocytes are very low, suggesting that the effects of lactogens might be mediated by other hormones or cellular growth factors. Our observations suggest roles for the lactogens in adipose tissue growth and metabolism in pregnancy and postnatal life.

Protein Phosphorylation and Protein-Protein Interactions

Intracellular signaling is the series of events which translates the specific message of circulating ligands into a particular biological response in target cells. The first step in hormone signaling involves the interaction between a ligand and its cognate receptor (membrane or nuclear), which in turn induces stoichiometric and conformational changes on the ligand-receptor complex. In the current state of the art, these modifications appear to be the molecular basis of signal triggering. Whatever the number or the type of proteins involved in signal transduction process within the cell, all known cascades involve one or, in most cases, two basic mechanisms: protein-protein interactions and protein phosphorylation.

Growth Hormone Receptor Signaling and Differential Actions in Target Tissues Compared to IGF-I

Growth hormone (GH) and IGF-I bind to specific membrane-bound receptors located in widely distributed target tissues. Although initial post-receptor signal transduction pathways differ - GH: associated tyrosine kinase (Jak) that activates signal transducers and activators of transcription (Stat) transcription factors; IGF-I: intrinsic tyrosine kinase that activates insulin receptor substrate (IRS) docking proteins, involved in several down stream effector pathways - many of the pathways are overlapping for GH and IGF-I, which makes it sometimes difficult to determine which hormone is responsible for the action being evaluated.