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 ∼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.

Prolactin upregulates its receptors and inhibits lipolysis and leptin release in male rat adipose tissue

“…In this study, both receptor isoforms were dramatically induced in epididymal preadipocytes during adipogenesis. A marked increase in total PRLR expression during adipocyte differentiation was also observed by others [14,15,16]. Regardless of the expression level of the PRLR, PRL further increased the expression of both isoforms (Fig 2).…”

Lipoatrophy in GH deficient patients treated with a long-acting pegylated GH

“…GH stimulates lipolysis in mature adipocytes and primary preadipocytes but promotes adipogenesis in preadipocyte cell lines. Mouse prolactin and mouse GH stimulate IGF1 mRNA in differentiated cells but not in undifferentiated cells (18,19). GH increases lipolysis as a direct effect of GH on adipocytes, as well as a decrease of lipoprotein lipase activity, diminishing the flow of fatty free acids to the adipocyte.…”

The growth hormone–insulin-like growth factor-I axis in chronic kidney disease

“…Following improvement in adipose tissue mass induced by AgRP, there was normalization of IGF-I but not myostatin gene expression [70]. This was not surprising, since IGF-I signaling is associated with adipogenesis [71], whereas there is no current information on the role of myostatin in adipose tissue.…”