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The Journal of Clinical Endocrinology & Metabolism Vol. 88, No. 4 1804-1808
Copyright © 2003 by The Endocrine Society

Identification of Functional Prolactin (PRL) Receptor Gene Expression: PRL Inhibits Lipoprotein Lipase Activity in Human White Adipose Tissue

Charlotte Ling, Louise Svensson, Birgitta Odén, Birgitta Weijdegård, Barbro Edén, Staffan Edén and Håkan Billig

Department of Physiology (C.L., L.S., S.E., H.B.), The Wallenberg Laboratory (B.O.), and Department of Obstetrics and Gynecology (B.W., B.E.), Sahlgrenska University Hospital, Göteborg University, 405 30 Göteborg, Sweden

Address all correspondence and requests for reprints to: Dr. Håkan Billig, Department of Physiology, Göteborg University, P.O. Box 434, SE 405 30 Göteborg, Sweden. E-mail: hakan.billig{at}fysiologi.gu.se.


   Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
During lactation serum levels of prolactin (PRL) are elevated, and the activity of lipoprotein lipase (LPL) is decreased in the adipose tissue and increased in the mammary gland. However, PRL has been suggested to affect the adipose tissue in an indirect fashion during lactation. In the present study, we demonstrated expression of four PRL receptor (PRLR) mRNA isoforms (L, I, S1a, and S1b) in human sc abdominal adipose tissue and breast adipose tissue using RT-PCR/Southern blot analysis. In addition, L-PRLR [relative molecular mass (Mr) 90,000] and I-PRLR (Mr 50,000) protein expression was detected in human sc abdominal adipose tissue and breast adipose tissue using immunoblot analysis. Two additional protein bands with the molecular weight Mr 40–35,000 were also detected. The direct effect of PRL on the regulation of LPL activity in human abdominal adipose tissue cultured in vitro was investigated. PRL (500 ng/ml) reduced the LPL activity in human adipose tissue to 31 ± 7.7%, compared with control. GH (100 ng/ml) also reduced the LPL activity, to 45 ± 8.6%, compared with control. In agreement with previous studies, cortisol increased the LPL activity and GH inhibited cortisol-induced LPL activity. Furthermore, we found that PRL also inhibited the cortisol-induced LPL activity. Taken together, these results demonstrate a direct effect of PRL, via functional PRLRs, in reducing the LPL activity in human adipose tissue, and these results suggest that LPL might also be regulated in this fashion during lactation.


   Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
THE ANTERIOR PITUITARY hormone, prolactin (PRL), is involved in a large number of physiological functions (1). PRL is an important factor in both mammary gland development and lactation (1). Lactation induces changes in metabolism of the mammary gland and other organs (2, 3, 4). For example, lipoprotein lipase (LPL) activity was found to increase in the mammary gland and decrease in adipose tissue during lactation (5, 6, 7). LPL is an enzyme bound to the heparan sulfate proteoglycans in capillary walls and it hydrolyzes triglycerides in chylomicrons and very low-density lipoproteins to remove triglycerides from the circulation and provide free fatty acids to different tissues (8, 9, 10). The net result of the changes of LPL activity during lactation is that triglycerides available in the circulation are directed to the mammary gland rather than to adipose tissue (11). PRL was suggested to regulate the LPL activity during lactation, and removal of litter, hypophysectomy, and bromocriptine treatment of lactating rats all resulted in a decrease of LPL activity in the mammary gland and an increase in the adipose tissue (3, 5, 6). PRL treatment reversed these effects. However, researchers reported that the effects of PRL on adipose tissue metabolism during lactation were dependent on a functional mammary gland, and they suggested that PRL might act on the adipose tissue in an indirect fashion (3). Furthermore, in a different study, insulin was reported to be the major regulator of lipid deposition in adipose tissue during lactation (12).

Numerous studies indicate that PRL plays a role in adipose tissue regulation and distribution. For example, hyperprolactinemia was found to reduce the weight of adipose tissue in mice (13, 14). PRL has also been demonstrated to affect insulin binding and glucose uptake in adipocytes of both humans and rodents (15, 16). In addition, PRL was found to increase leptin secretion in vivo and reduce insulin-induced leptin secretion in adipocytes cultured in vitro (13, 17, 18). Detection of PRL receptor (PRLR) expression has been technically difficult in adipose tissue because of the properties of the tissue. In a previous study, PRLR expression could not be demonstrated in rat adipocytes, and PRL was therefore suggested to affect adipose tissue metabolism indirectly (3). However, with the development of more sensitive assays, we recently demonstrated PRLR mRNA and protein expression in mouse adipose tissue (13). PRLR expression increased in white adipose tissue of wild-type lactating mice and PRL-transgenic mice, compared with controls (13). Furthermore, PRL increased cytokine inducible SH2-domain-containing protein mRNA expression and suppressed insulin-induced leptin secretion in female mouse adipocytes cultured in vitro, demonstrating PRLR mediated direct effects in mouse adipocytes (19). In addition, PRLR expression was recently demonstrated in the stroma of the rat mammary gland (20). However, PRLR expression has not been investigated in white adipose tissue of humans.

The PRLR is a member of the cytokine receptor superfamily (1). Multiple PRLR isoforms that differ mainly in their intracellular domains have been identified, and the isoforms vary between species. In humans, a long (L), an intermediate (I), and two short (S1a and S1b) PRLR isoforms have been observed (21, 22, 23). The nucleotide sequence of the human I-PRLR is identical to the L-PRLR up to bp 1009, where a deletion of 573 nucleotides occurs, juxtaposing bp 1009 to 1583 (22). The human S1a- and S1b-PRLR are derived from alternative splicing between exon 10 and a recently identified exon 11 (23).

The aim of this study was to determine whether four different PRLR isoforms are expressed in human sc abdominal adipose tissue and in adipose tissue from human breast and whether PRL directly regulates the LPL activity in human adipose tissue.


   Subjects and Methods
Top
 Abstract
 Introduction
 Subjects and Methods
Results
 Discussion
 References
 
Subjects

Breast adipose tissue was obtained from seven healthy women aged 18–58 yr (38.8 ± 5.3) with body mass index (BMI) 24.3 ± 0.8 undergoing breast reduction. The breast adipose tissue was fresh frozen in liquid nitrogen and stored at -70 C until the time of RNA and protein preparations. Subcutaneous abdominal adipose tissue was obtained from another eight women. Of these, four women were aged 30–50 yr (42 ± 6) with BMI 24.3 ± 1.2, and the sc abdominal adipose tissue was fresh frozen in liquid nitrogen and stored at -70 C until the time of RNA and protein preparations. One of these subjects was treated with an estradiol antagonist (tamoxifen), and three were healthy subjects. The remaining sc abdominal adipose tissue was obtained from four healthy fertile women aged 32–49 yr (37.5 ± 4) with BMI 26.1 ± 1.7, and from these subjects pieces of adipose tissue (5–20 mg each) were prepared under sterile conditions and incubated in vitro in polypropylene tubes (500 mg tissue/20 ml medium). PRLR expression studies were performed on breast adipose tissue from seven women and sc abdominal adipose tissue from eight women. The study was approved by the Ethics Committee of Göteborg University.

RNA extraction

Total RNA was extracted from frozen tissues using Tri Reagent according to the manufacturer’s instructions (Sigma, St. Louis, MO).

RT-PCR and Southern blot analysis

The reverse transcription reaction was performed using 2 µg total RNA together with 2.5 µM oligo (deoxythymidine) primer (Promega Corp., Madison, WI). The mixture was denatured at 70 C for 5 min and then placed on ice, before 1x reverse transcription buffer (Promega Corp.), 0.5 mM deoxynucleotide triphosphate, 20 U Rnasin (Promega Corp.), and 200 U Moloney murine leukemia virus reverse transcriptase (Promega Corp.) were added to a total reaction volume of 25 µl. The cDNA synthesis was then carried out at 42 C for 60 min.

To analyze the expression of L-PRLR and I-PRLR, the primer pair [upstream primer: hPRLRa, 5'-AGTGGCTTTGAAGGGCTAT-3' (nucleotides 1049–1067) (21) and downstream primer: hPRLRb, 5'-AGGAGTCCCGGGCTT-3' (nucleotides 1890–1905) (21), generating an 856-bp L-PRLR DNA fragment and a 284-bp I-PRLR DNA fragment] was used in a PCR reaction (94 C for 2 min and then 32 cycles of sequential incubations at 94 C for 45 sec, 60 C for 1 min, and 72 C for 1 min, and finally 72 C for 7 min). The PCR products were verified by Southern blot analysis using a random-prime [32P]-dCTP-labeled probe (Megaprime labeling kit, Pharmacia, Uppsala, Sweden) made from a PRLR DNA template (nucleotides 1148–1391), which recognizes both L- and I-PRLR. In addition, the 856-bp L-PRLR PCR product was verified by DNA sequencing.

To analyze the expression of S1a-PRLR and S1b-PRLR, the following primer pair, hP23 and hP44 (23), generating a 460-bp S1a DNA fragment and a 306-bp S1b DNA fragment, was used in a PCR reaction (94 C for 2 min and then 35 cycles of sequential incubations at 94 C for 45 sec, 55 C for 1 min, and 72 C for 1 min, and finally 72 C for 7 min). The PCR products were verified by Southern blot analysis using a random-prime [32P]-dCTP-labeled probe (Megaprime labeling kit, Pharmacia) made from a PRLR DNA template (nucleotides 1049–1391), which recognizes both S1a- and S1b-PRLR. In addition, the 460-bp S1a- and the 306-bp S1b-PRLR PCR products were verified by DNA sequencing.

Protein extraction and immunoblotting

Protein extraction from sc abdominal and breast adipose tissue was performed as previously reported (13). Twenty micrograms of total protein were loaded in each lane on SDS-polyacrylamide gels (4–12% NuPage gels, MOPS buffer; Novex, San Diego, CA). A prestained standard (MultiMark; Novex) was used as a weight marker. The proteins were then transferred to polyvinyldiflouride membranes (Amersham International, Buckinghamshire, UK). Thereafter the membrane was incubated with either a specific antibody against the extracellular part of the hPRLR (4 C overnight, 7770–6010, dilution 1:1,000; Biogenesis, Poole, UK), washed in WBI and WBII, and incubated with antisheep antibody linked to alkaline phosphatase (2 h, dilution 1:30,000; Sigma), or a specific antibody against the human I-PRLR (4 C overnight, 34–4800, dilution 1:167; Zymed Laboratories, Inc. Corp., San Francisco, CA), washed in WBI and WBII, and incubated with antirabbit antibody linked to alkaline phosphatase (2 h, dilution 1:30,000; Tropix, Bedford, MA). Immunoreactive protein was visualized by chemiluminescence using CDP-Star as substrate (Tropix). The membrane was exposed to ECL film (Amersham) at room temperature for 10–90 sec and subsequently developed in a Curix 60 developing machine (AGFA-Geveart AG, München, Germany).

Adipose tissue in vitro culture and hormonal treatment

Pieces of human adipose tissue (5–20 mg each) were cultured in vitro for 6 d as previously described (24). In vitro incubations were performed four times using adipose tissue from one woman each time, and in each hormonal treatment, there were duplicate samples. The tissue (12 samples at each incubation) was first preincubated for 3 d in control medium (modified Parker 199 medium, SBL Vaccin AB, Stockholm, Sweden) containing 1 mU insulin (Actrapid, Novo Nordisk Scandinavia AB, Malmö, Sweden) and 0.1 mg/ml Keflin (Eli Lilly & Co., Indianapolis, IN). Insulin and Keflin were present in all samples for the rest of the incubation. Culture medium was changed once per day. During the next 2 d, the tissue was incubated without (six samples, treatment group 1–3) or with (six samples, treatment group 4–6) 1 µM cortisol (hydrocortisone, Sigma). For the last 24 h, six different treatment groups were studied (n = 2 per treatment): 1) control medium; 2) control medium + hPRL [500 ng/ml (recombinant hPRL AFP795; National Hormone and Peptide Program, Baltimore, MD)]; 3) control medium + hGH [100 ng/ml (Norditropin, Novo Nordisk, Gentofte, Denmark)]; 4) cortisol; 5) cortisol + hPRL (500 ng/ml); and 6) cortisol + hGH (100 ng/ml).

LPL activity

The LPL activity was analyzed in adipose tissue samples cultured in vitro as previously described (24, 25).

Statistical analysis

Differences in relative LPL activity among groups were analyzed using one-way ANOVA, followed by the Student-Newman-Keuls multiple range test.


   Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
PRLR mRNA expression in human sc abdominal adipose tissue and breast adipose tissue

To examine whether PRLR mRNA is expressed in human sc abdominal adipose tissue and breast adipose tissue, an RT-PCR that will distinguish between the L- and I-PRLR isoforms was performed (Fig. 1AGo). Two mRNA species of 856 and 284 bp corresponding to the L-PRLR and I-PRLR isoforms were amplified from the sc abdominal and breast adipose tissue as indicated by Southern blot analysis (Fig. 1AGo). The ovary was used as a positive control.



View larger version (47K):
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  		Figure 1. Analysis of four different hPRLR mRNA isoforms (L, I, S1a, and S1b) in human breast adipose tissue (Breast AT), sc abdominal adipose tissue (WAT), and ovary using RT-PCR, followed by Southern blot analysis. A, Detection of L- (856 bp) and I-PRLR (284 bp) by RT-PCR using the hPRLRa- and hPRLRb-primer, followed by Southern blot analysis using a 32P-labeled probe (nucleotides 1148–1391) that recognizes both L- and I-PRLR. B, Detection of S1a- (460 bp) and S1b-PRLR (306 bp) by RT-PCR using the hP23- and hP44-primer (23 ), followed by Southern blot analysis using a 32P-labeled probe (nucleotides 1049–1391) that recognizes both S1a- and S1b-PRLR.

 
To determine whether the two short isoforms, S1a- and S1b-PRLR, are also expressed in human sc abdominal and breast adipose tissue, an RT-PCR that will distinguish between the two short isoforms was performed (Fig. 1BGo). Two mRNA species of 460 and 306 bp corresponding to the S1a- and S1b-PRLR isoforms were amplified from the sc abdominal and breast adipose tissue as indicated by Southern blot analysis (Fig. 1BGo). The ovary was used as a positive control.

PRLR protein expression in human sc abdominal adipose tissue and breast adipose tissue

Immunoblot studies were performed to examine PRLR protein expression in human sc abdominal and breast adipose tissue. Two different human PRLR antibodies were used. The antibody used in the first immunoblot (Fig. 2AGo) recognizes the extracellular part of the hPRLR, and it can therefore detect L-, I-, S1a-, and S1b-PRLR. This immunoblot revealed a protein with the relative molecular mass (Mr) 90,000, corresponding to L-PRLR, in human sc abdominal adipose tissue, breast adipose tissue, and ovary (Fig. 2AGo). In addition, Mr 50,000 protein bands were detected in both the sc abdominal and breast adipose tissue (Fig. 2AGo). In a previous study, the I-PRLR isoform was demonstrated to be an Mr 50,000 protein (22). The immunoblot also detected Mr 40,000 and Mr 35,000 protein bands in the samples analyzed (Fig. 2AGo). An additional antibody that recognizes only the I-PRLR was used (Fig. 2BGo). This antibody detected Mr 50,000 proteins in human sc abdominal adipose tissue, breast adipose tissue, and ovary (Fig. 2BGo).



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  		Figure 2. Immunoblot analysis of hPRLR protein expression in human breast adipose tissue (Breast AT), sc abdominal adipose tissue (WAT), and the ovary. A, A hPRLR antibody that recognizes an epitope in the extracellular domain of the hPRLR was used (7770–6010; Biogenesis). Positions of the Mr 90,000 band (L-PRLR), Mr 50,000 band (I-PRLR), approximately Mr 40,000 band, and approximately Mr 35,000 band (possibly the S1a- and S1b-PRLR) are indicated. B, An antibody that recognizes an epitope specific to the human I-PRLR was used (34–48000; Zymed Laboratories, Inc. Corp.). Position of the Mr 50,000 band (I-PRLR) is indicated.

 
Hormonal regulation of LPL activity in human adipose tissue cultured in vitro

The LPL activity was analyzed in human adipose tissue treated with PRL (500 ng/ml) or GH (100 ng/ml) for 24 h after 5 d of incubation in control medium. PRL reduced the LPL activity to 31% ± 7.7%, compared with the control (Fig. 3AGo). Addition of GH (100 ng/ml) for 24 h also reduced the LPL activity, to 45% ± 8.6%, compared with the control (Fig. 3AGo). Furthermore, PRL’s ability to lower LPL activity already induced by cortisol was analyzed. As previously described (24), treatment with cortisol (1 µM) for 3 d after 3 d of preincubation increased the LPL activity dramatically (1440% ± 308%) in the adipose tissue, compared with the control, and addition of GH for the last 24 h inhibited the cortisol-induced LPL activity (Fig. 3BGo). When PRL was present together with cortisol during the last 24 h of adipose tissue incubation, PRL also inhibited the cortisol-induced LPL activity (Fig. 3BGo).



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  		Figure 3. The direct effects of PRL on LPL activity in human adipose tissue cultured in vitro. Human adipose tissue was incubated for 6 d. A, During the last 24 h, the following hormonal treatments were studied: control (no hormone added), hPRL (500 ng/ml), and hGH (100 ng/ml). B, During the last 24 h, the following hormonal treatments were studied: control (no hormone added), cortisol (1 µM), cortisol plus hPRL (1 µM cortisol, and 500 ng/ml hPRL), and cortisol plus hGH (1 µM cortisol and 100 ng/ml GH). For each incubation experiment, adipose tissue from one subject was used, and in each hormonal treatment, there were duplicate samples. The LPL activity was analyzed as previously described (24 25 ). The average LPL activity in the control was set at 100%. Results are expressed as the mean ± SEM (each bar represents eight individual cultures derived from four patients), and bars with different superscripts are significantly different from each other (P < 0.05), using one-way ANOVA, followed by Student-Newman-Keuls multiple range test.

 

   Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
Although several reports demonstrate that PRL influences adipose tissue metabolism, controversy has existed as to whether PRL mediates these effects directly or indirectly in human adipose tissue, and PRLR expression has previously not been demonstrated in human adipose tissue. In the present study, we demonstrated expression of four PRLR mRNA isoforms, L, I, S1a, and S1b, in human sc abdominal and breast adipose tissue. In addition, L-PRLR (Mr 90,000) and I-PRLR (Mr 50,000) as well as Mr 40–35,000 proteins were examined in all samples analyzed. These results open the possibility for direct effects of PRL on human adipose tissue.

Differential tissue expression of human L-PRLR and I-PRLR mRNA was demonstrated in a previous study. I-PRLR was found to be the predominant isoform in bone marrow, heart, small intestine, spleen, and skeletal muscle, and L-PRLR was the predominant isoform in colon, liver, stomach, and placenta (22). In the present study, we found no difference in L- and I-PRLR mRNA expression in human sc abdominal, compared with breast adipose tissue of healthy women using realtime PCR, TaqMan (data not shown). However, it is possible that a different expression pattern would be seen in sc abdominal, compared with breast, adipose tissue from pregnant and lactating women or patients with hyperprolactinemia. Furthermore, researchers have investigated differences in signaling and biological effects of L-PRLR compared with I-PRLR. The L-PRLR can activate several signaling pathways, including the Janus kinase 2/signal transducer and activator of transcription 5 and MAPK pathway, and L-PRLR has been suggested to account for many of PRL’s biological effects. I-PRLR differs in both its signaling pathway and biological activity, compared with L-PRLR. In response to PRL, I-PRLR-transfected cells generated equivalent levels of Janus kinase 2 activation but only minimal activation of Fyn, compared with L-PRLR-transfected cells (22). Furthermore, I-PRLR transfectants exhibited modest proliferation, compared with L-PRLR transfectants, but both receptor isoforms were equivalent in their inhibition of apoptosis (22).

Two short human PRLR isoforms, S1a and S1b, were recently identified (23). When the S1a- and S1b-PRLR were expressed in COS-1 and human embryonic kidney 293 cells, proteins of 56 and 42 kDa were detected (23). However, the calculated molecular weight of S1a- and S1b-PRLR proteins is 39 kDa and 29 kDa, respectively. This study is the first to analyze endogenous S1a and S1b protein expression in human tissues. In addition to L- and I-PRLR protein bands, the immunoblot detected ~40 kDa and ~35 kDa protein bands in human sc abdominal adipose tissue, breast adipose tissue, and the ovary. The identity of these 40-kDa and 35-kDa protein bands is not clear. However, because S1a- and S1b-PRLR mRNA expression was detected in human adipose tissue, breast adipose tissue, and the ovary, it is also likely that the respective protein is expressed in these tissues. Human S1a- and S1b-PRLR have been demonstrated to act as dominant negative forms when coexpressed with L-PRLR in transfected cells (23). Furthermore, neither short form was able to mediate activation of the ß-casein promoter induced by PRL (23). In resemblance to L- and I-PRLR mRNA, we found that neither S1a- nor S1b-PRLR mRNA was differentially expressed in sc abdominal, compared with breast, adipose tissue (data not shown). However, the biological functions of the different PRLR isoforms need further investigation in numerous human tissues.

The direct effects of PRL on LPL activity in human adipose tissue cultured in vitro were investigated in this study. PRL reduced the LPL activity in human adipose tissue, compared with the control. Furthermore, PRL also inhibited cortisol-induced LPL activity. During lactation there are reciprocal changes in the LPL activity in adipose tissue and the mammary gland (5, 6, 26). PRL was for a long time suggested to regulate these changes in LPL activity during lactation (11). However, when PRLR could not be demonstrated in rat adipocytes, PRL was suggested to regulate adipose tissue LPL activity in an indirect fashion (3). Our findings demonstrate that PRL affects the LPL activity in human adipose tissue in a direct fashion via functional PRLRs and PRL might therefore also regulate the LPL activity in human adipose tissue during lactation.

In summary, this study demonstrates expression of four PRLR isoforms in human abdominal adipose tissue, thereby providing a direct route for regulation of human adipose tissue by PRL. PRLRs were also detected in human breast adipose tissue. In addition, PRL was shown to directly affect and inhibit the LPL activity in human adipose tissue via functional PRLRs, suggesting an important role for PRL in regulating adipose tissue metabolism during lactation.


   Footnotes
 
This work was supported by Grants 10380 and 13550 from the Swedish Medical Research Council and grants from The Royal Society of Arts and Sciences in Göteborg, The Swedish Society for Medical Research, and Assar Gabrielsson’s research fund.

C.L. and L.S. were equal contributors to this work.

Abbreviations: BMI, Body mass index; I, intermediate prolactin receptor isoform; L, long prolactin receptor isoform; Mr, relative molecular mass; LPL, lipoprotein lipase; PRL, prolactin; PRLR, PRL receptor; S1a and S1b, PRLR isoforms.

Received July 23, 2002.

Accepted January 8, 2003.


   References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

  1. Bole-Feysot C, Goffin V, Edery M, Binart N, Kelly PA 1998 Prolactin (PRL) and its receptor: actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice. Endocr Rev 19:225–268[Abstract/Free Full Text]
  2. Ros M, Lobato MF, Garcia-Ruiz JP, Moreno FJ 1990 Integration of lipid metabolism in the mammary gland and adipose tissue by prolactin during lactation. Mol Cell Biochem 93:185–194[Medline]
  3. Flint DJ, Clegg RA, Vernon RG 1981 Prolactin and the regulation of adipose-tissue metabolism during lactation in rats. Mol Cell Endocrinol 22:265–275[CrossRef][Medline]
  4. Agius L, Robinson AM, Girard JR, Williamson DH 1979 Alterations in the rate of lipogenesis in vivo in maternal liver and adipose tissue on premature weaning of lactating rats: a possible regulatory role of prolactin. Biochem J 180:689–692[Medline]
  5. Hamosh M, Clary TR, Chernick SS, Scow RO 1970 Lipoprotein lipase activity of adipose and mammary tissue and plasma triglyceride in pregnant and lactating rats. Biochim Biophys Acta 210:473–482[Medline]
  6. Zinder O, Hamosh M, Fleck TR, Scow RO 1974 Effect of prolactin on lipoprotein lipase in mammary glands and adipose tissue of rats. Am J Physiol 226:742–748[Medline]
  7. Jensen DR, Gavigan S, Sawicki V, Witsell DL, Eckel RH, Neville MC 1994 Regulation of lipoprotein lipase activity and mRNA in the mammary gland of the lactating mouse. Biochem J 298:321–327
  8. Eckel RH 1989 Lipoprotein lipase: a multifunctional enzyme relevant to common metabolic disease. N Engl J Med 320:1060–1068[Abstract]
  9. Goldberg IJ 1996 Lipoprotein lipase and lipolysis: central roles in lipoprotein metabolism and atherogenesis. J Lipid Res 37:693–707[Abstract]
  10. Zechner R, Strauss J, Frank S, Wagner E, Hofmann W, Kratky D, Hiden M, Levak-Frank S 2000 The role of lipoprotein lipase in adipose tissue development and metabolism. Int J Obes Relat Metab Disord 24(Suppl 4):S53–S56
  11. Williamson DH 1980 Integration of metabolism in tissues of lactating rat. FEBS Lett 117:93–105[CrossRef][Medline]
  12. Oller do Nascimento CM, Ilic V, Williamson DH 1989 Re-examination of the putative roles of insulin and prolactin in the regulation of lipid deposition and lipogenesis in vivo in mammary gland and white and brown adipose tissue of lactating rats and litter-removed rats. Biochem J 258:273–278[Medline]
  13. Ling C, Hellgren G, Gebre-Medhin M, Dillner K, Wennbo H, Carlsson B, Billig H 2000 Prolactin (PRL) receptor gene expression in mouse adipose tissue: increases during lactation and in PRL-transgenic mice. Endocrinology 141:3564–3572[Abstract/Free Full Text]
  14. Matsuda M, Mori T, Sassa S, Sakamoto S, Park MK, Kawashima S 1996 Chronic effect of hyperprolactinemia on blood glucose and lipid levels in mice. Life Sci 58:1171–1177[CrossRef][Medline]
  15. Jarrett JCN, Ballejo G, Saleem TH, Tsibris JC, Spellacy WN 1984 The effect of prolactin and relaxin on insulin binding by adipocytes from pregnant women. Am J Obstet Gynecol 149:250–255[Medline]
  16. Ryan EA, Enns L 1988 Role of gestational hormones in the induction of insulin resistance. J Clin Endocrinol Metab 67:341–347[Abstract]
  17. Gualillo O, Lago F, Garcia M, Menendez C, Senaris R, Casanueva FF, Dieguez C 1999 Prolactin stimulates leptin secretion by rat white adipose tissue. Endocrinology 140:5149–5153[Abstract/Free Full Text]
  18. Freemark M, Fleenor D, Driscoll P, Binart N, Kelly P 2001 Body weight and fat deposition in prolactin receptor-deficient mice. Endocrinology 142:532–537[Abstract/Free Full Text]
  19. Ling C, Billig H 2001 PRL receptor-mediated effects in female mouse adipocytes: PRL induces suppressors of cytokine signaling expression and suppresses insulin-induced leptin production in adipocytes in vitro. Endocrinology 142:4880–4890[Abstract/Free Full Text]
  20. Camarillo IG, Thordarson G, Moffat JG, Van Horn KM, Binart N, Kelly PA, Talamantes F 2001 Prolactin receptor expression in the epithelia and stroma of the rat mammary gland. J Endocrinol 171:85–95[Abstract]
  21. Boutin JM, Edery M, Shirota M, Jolicoeur C, Lesueur L, Ali S, Gould D, Djiane J, Kelly PA 1989 Identification of a cDNA encoding a long form of prolactin receptor in human hepatoma and breast cancer cells. Mol Endocrinol 3:1455–1461[Abstract]
  22. Kline JB, Roehrs H, Clevenger CV 1999 Functional characterization of the intermediate isoform of the human prolactin receptor. J Biol Chem 274:35461–35468[Abstract/Free Full Text]
  23. Hu ZZ, Meng J, Dufau ML 2001 Isolation and characterization of two novel forms of the human prolactin receptor generated by alternative splicing of a newly identified exon 11. J Biol Chem 276:41086–41094[Abstract/Free Full Text]
  24. Ottosson M, Vikman-Adolfsson K, Enerback S, Elander A, Bjorntorp P, Eden S 1995 Growth hormone inhibits lipoprotein lipase activity in human adipose tissue. J Clin Endocrinol Metab 80:936–941[Abstract]
  25. Ottosson M, Vikman-Adolfsson K, Enerback S, Olivecrona G, Bjorntorp P 1994 The effects of cortisol on the regulation of lipoprotein lipase activity in human adipose tissue. J Clin Endocrinol Metab 79:820–825[Abstract]
  26. Fielding BA, Frayn KN 1998 Lipoprotein lipase and the disposition of dietary fatty acids. Br J Nutr 80:495–502[CrossRef][Medline]



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