title: Growth hormone and prolactin receptors in adipogenesis: STAT-5 activation, suppressors of cytokine signaling, and regulation of insulin-like growth factor I.
abstract: Growth hormone GH stimulates lipolysis in mature adipocytes and primary preadipocytes but promotes adipogenesis in preadipocyte cell lines. The lactogenic hormones (prolactin PRL and placental lactogen) also stimulate adipogenesis in preadipocyte cell lines but have variable lipolytic and lipogenic effects in mature adipose tissue. We hypothesized that differences in expression of GH receptors GHR and PRL receptors PRLR during adipocyte development might explain some of the differential effects of the somatogens and lactogens on fat metabolism. To that end, we compared: (a) the expression of GHR and PRLR mRNAs in 3T3-L1 preadipocytes during the course of adipocyte differentiation; (b) the induction of STAT-5 activity by GH and PRL during adipogenesis; and (c) the acute effects of GH and PRL on the suppressors of cytokine signaling (SOCS-1-3 and cytokine-inducible SH2-domain-containing protein CIS) and IGF-I. In confluent, undifferentiated 3T3-L1 cells, the levels of GHR mRNA were approximately 250-fold higher than the levels of PRLR mRNA. Following induction of adipocyte differentiation the levels of PRLR mRNA rose 90-fold but GHR mRNA increased only 0.8-fold. Expression of both full-length (long) and truncated (short) isoforms of the PRLR increased during differentiation but the long isoform predominated at all time points. Mouse GH mGH stimulated increases in STAT-5a and 5b activity in undifferentiated as well as differentiating 3T3-L1 cells; mouse PRL mPRL had little or no effect on STAT-5 activity in undifferentiated cells but stimulated increases in STAT-5a and 5b activity in differentiating cells. mGH stimulated increases in SOCS-2 and SOCS-3 mRNAs in undifferentiated cells and SOCS-1-3 and CIS mRNAs in differentiating cells; mPRL induced CIS in differentiating cells but had no effect on SOCS-1-3. mPRL and mGH stimulated increases in IGF-I mRNA in differentiating cells but not in undifferentiated cells; the potency of mGH (3-6-fold increase, p < 0.01) exceeded that of mPRL (40-90% increase, p < 0.05). Our findings reveal disparities in the expression of PRLR and GHR during adipocyte development and differential effects of the hormones on STAT-5, the SOCS proteins, CIS, and IGF-I. These observations suggest that somatogens and lactogens regulate adipocyte development and fat metabolism through distinct but overlapping cellular mechanisms.
authors.affiliation: Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA. fleen001@mc.duke.edu
authors.forename: Don
authors.initials: D
authors.lastname: Fleenor
authors.forename: Ramamani
authors.initials: R
authors.lastname: Arumugam
authors.forename: Michael
authors.initials: M
authors.lastname: Freemark
mesh_terms: D050156:Adipogenesis / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects*; D013006:Growth Hormone / Q000378:metabolism / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis; D050356:Lipid Metabolism / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D011388:Prolactin / Q000378:metabolism / Q000494:pharmacology; D011981:Receptors, Prolactin / Q000096:biosynthesis; D011986:Receptors, Somatotropin / Q000096:biosynthesis; D050799:STAT5 Transcription Factor / Q000096:biosynthesis; D050826:Suppressor of Cytokine Signaling Proteins / Q000096:biosynthesis
chemical_list: D011981:Receptors, Prolactin; D011986:Receptors, Somatotropin; D050799:STAT5 Transcription Factor; C494093:Stat5a protein, mouse; C494096:Stat5b protein, mouse; D050826:Suppressor of Cytokine Signaling Proteins; D007334:Insulin-Like Growth Factor I; D011388:Prolactin; D013006:Growth Hormone