The Library

Dydrogesterone and norethisterone regulate expression of lipoprotein lipase and hormones-sensitive lipase in human subcutaneous abdominal adipocytes

Tools

Palin, S. L., McTernan, P. G., McGee, K. C., Sturdee, D. W., Barnett, A. H. and Kumar, Sudhesh. (2007) Dydrogesterone and norethisterone regulate expression of lipoprotein lipase and hormones-sensitive lipase in human subcutaneous abdominal adipocytes. Diabetes, Obesity and Metabolism, Vol.9 (No.4). pp. 585-590. ISSN 1462-8902

Preview

PDF
WRAP_Kumar_2007_-_Post-print_version_Dydrogesterone_and_norethisterone_regulate.pdf - Draft Version - Requires a PDF viewer.
Download (130Kb)

Official URL: http://dx.doi.org/10.1111/j.1463-1326.2006.00680.x

Abstract

Aim: In premenopausal women, hyper-androgenicity is associated with central obesity and an increased cardiovascular risk. We investigated the effects of dydrogesterone (DYD)(a non-androgenic progestogen) and norethisterone (NET)(an androgenic progestogen) on lipoprotein lipase (LPL), hormone-sensitive lipase (HSL) and glycerol release in adipocytes isolated from subcutaneous abdominal adipose tissue. Methods: Adipose tissue was obtained from 12 non-diabetic women, mean age 51 years (range 37-78) and mean BMI 25.4kg/m2 (range 20.3-26.4). Adipocytes were treated with increasing doses of DYD and NET for 48 hours prior to protein extraction. Effects on lipogenesis and lipolysis were assessed using western blotting to determine the expression of key enzymes, LPL (56kDa) and HSL (84kDa) respectively. Measurement of glycerol release into the medium provided an assessment of lipolytic activity. Results: Expression of LPL was increased by DYD and NET (mean protein expression relative to control ± SEM); with greatest effect at 10-8M for DYD: 2.32±0.51(p<0.01) and 10-8M for NET: 2.06±0.19(p<0.01). In contrast, HSL expression was reduced by all concentrations of DYD, with maximal effect at 10-9M: 0.49±0.02(p<0.001). NET reduced HSL expression at all concentrations from 10-9M: 0.62±0.06(p<0.001) to 10-7M: 0.69±0.08(p<0.001). Glycerol measurements supported the HSL expression studies(p>0.05). Conclusions: DYD and NET significantly increased LPL expression relative to control whilst significantly reducing HSL expression. At the concentrations studied, similar effects were observed with the androgenic NET and the non-androgenic DYD despite differing effects on the lipid profile when taken
in combination with estrogen. Further work in this area may improve knowledge about the effects of different progestogens on body fat distribution and enable progestogen use to be tailored to the individual to achieve maximal benefits.

Item Type:

Journal Article

Subjects:

R Medicine > RM Therapeutics. Pharmacology

Divisions:

Faculty of Medicine > Warwick Medical School

Library of Congress Subject Headings (LCSH):

Adipose tissues, Fat cells, Menopause -- Hormone therapy

Journal or Publication Title:

Diabetes, Obesity and Metabolism

Publisher:

Blackwell

ISSN:

1462-8902

Official Date:

23 January 2007

Dates:

Date	Event
23 January 2007	Published

Volume:

Vol.9

Number:

No.4

Page Range:

pp. 585-590

Identifier:

10.1111/j.1463-1326.2006.00680.x

Status:

Not Peer Reviewed

Access rights to Published version:

Open Access

Description:

Version accepted by publisher (post-print, after peer review, before copy-editing).

Related URLs:

http://www3.interscience.wiley.com/cgi-b...

References:

[1] Barrett-Connor E, Wingard DL, Criqui MH. Postmenopausal estrogen use and heart disease risk factors in the 1980s. JAMA 1989; 261: 2095-2100.
[2] Lobo RA. Effects of hormonal replacement on lipids and lipoproteins in postmenopausal women. J Clin Endocrinol Metab 1991; 73: 925-930.
9
[3] Walsh BW, Schiff I, Rosner B, Greenburg L, Ravnikar V, Sacks FM. Effects of postmenopausal estrogen replacement on the concentrations and metabolism of plasma lipoproteins. N Engl J Med 1991; 325: 1196-1203.
[4] Nabulsi AA, Folsom A, White A, et al. Associations of hormone replacement therapy with various cardiovascular risk factors for post-menopausal women. N Engl J Med 1993; 328: 1069-1075.
[5] The Writing Group for the PEPI Trial. Effects of estrogen/progestin regimens on heart disease risk factors in post-menopausal women. JAMA 1995; 273: 199-208.
[6] Davis SR., Walker KZ, Strauss BJG. Effects of estradiol with and without testosterone on body composition and relationships with lipids in postmenopausal women. Menopause 2000; 7: 395-401.
[7] Ley CJ, Lees B, Stevenson JC. Sex- and menopause-associated changes in body-fat distribution. Am J Clin Nutr 1992; 55: 950-954.
[8] Lapidus L, Bengtsson C, Larsson B, Pennert K, Ryb E, Sjostrom L. Distribution of adipose tissue and risk of cardiovascular disease and death: a 12 year follow up of participants in the population study of women in Gothenberg, Sweden. BMJ 1984; 289: 1257-1261.
[9] Barrett-Connor E, Khaw K-T. Endogenous sex hormones and cardiovascular disease in men. A prospective population-based study. Circulation 1988; 78: 539-545.
[10] Seidell J, Bjorntorp P, Sjostrom L, Kvist H, Sannerstedt, R. Visceral fat accumulation in men is positively associated with insulin, glucose and C-peptide levels, but negatively with testosterone levels. Metabolism 1990; 39: 897-901.
10
[11] Marin P, Holmang S, Jonsson L, et al. The effects of testosterone treatment on body composition and metabolism in middle-aged obese men. Int J Obes 1992; 16: 991-997.
[12] Evans DJ, Hoffmann RG, Kalkhoff RK, Kissebah AH. Relationship of androgenic activity to body fat topography, fat cell morphology, and metabolic abberations in premenopausal women. J Clin Endocrinol Metab 1983; 57: 304-310.
[13] Grady D, Gebretsadik J, Kerlikowske K, Ernster V, Petitti D. Hormone replacement therapy and endometrial cancer risk: a meta-analysis. Obstet Gynecol 1995; 85: 304-313.
[14] Godsland IF. Effects of postmenopausal hormone replacement therapy on lipid, lipoprotein, and apolipoprotein (a) concentrations: analysis of studies published from 1974-2000. Fertil Steril 2001; 75: 898-915.
[15] European Progestin Club. Progestins: Present and Future. J Steroid Biochem Molec Biol 1996; 59: 357-363.
[16] Haarbo J, Marslew U, Gotfredsen A, Christiansen C. Postmenopausal hormone replacement therapy prevents central distribution of body fat after menopause. Metabolism 1991; 12: 1323-1326.
[17] Reubinoff BE, Wurtman J, Rijanshky N, et al. Effects of hormone replacement therapy on weight, body composition, fat distribution, and food intake in early postmenopausal women: a prospective study. Fertil Steril 1995; 64: 963-968.
[18] Hanggi W, Lippuner K, Jaeger P, Birkhauser MH, Horber FF. Differential impact of conventional oral or transdermal hormone replacement therapy or tibolone on body composition in postmenopausal women. Clin Endocrinol 1998: 48: 691-699.
11
[19] Kim H-J, Kalkhoff RK. Sex steroid influence on triglyceride metabolism. J Clin Invest 1975; 56: 888-896.
[20] Steingrimsdottir L, Brasel J, Greenwood MRC. Hormonal modulation of adipose tissue lipoprotein lipase may alter food intake in rats. Am J Physiol 1980; 239: E162-E167.
[21] Shirling D, Ashby JP, Baird JD. Effect of progesterone on lipid metabolism in the intact rat. J Endocrinol 1981; 90: 285-294.
[22] Valette A, Verine A, Varesi L, Boyer J. Effects of ethynyl estradiol and progesterone on triglyceride metabolism in the female rat. Endocrinol 1978; 103: 1647-1653.
[23] Rebuffe-Scrive M, Basdevant A, Guy-Grand B. Effect of local application of progesterone on human adipose tissue lipoprotein lipase. Horm Metabol Res 1983; 15: 566.
[24] Rebuffe-Scrive M, Lonnroth P, Marin P, Wesslau C, Bjorntorp P, Smith, U. Regional adipose tissue metabolism in men and postmenopausal women. Int J Obes 1987; 11: 347-355.
[25] Rebuffe-Scrive M. Sex steroid hormones and adipose tissue metabolism in ovariectomized and adrenalectomized rats. Acta Physiol Scand 1987; 129: 471-477.
[26] Lindberg U-B, Crona N, Silfverstolpe G, Bjorntorp P, Rebuffe-Scrive M. Regional adipose tissue metabolism in postmenopausal women after treatment with exogenous sex steroids. Horm Metabol Res 1990; 22: 345-351.
[27] McTernan PG, Anwar A, Eggo MC, Barnett AH, Stewart PM, Kumar S. Gender differences in the regulation of P450 aromatase expression and activity in human adipose tissue. Int J Obesity 2000; 24: 875-881.
12
[28] Palin SL, McTernan PG, Anderson LA, Sturdee DW, Barnett AH, Kumar S. 17β-estradiol and anti-estrogen ICI: compound 182,780 regulate expression of lipoprotein lipase and hormone-sensitive lipase in isolated subcutaneous abdominal adipocytes. Metabolism 2003; 52: 383-388.
[29] Green A, Dobias SB, Walter DJA, Brasier AR. Tumour necrosis factor increases the rate of lipolysis in primary cultures of adipocytes by a novel mechanism. Endocrinology 1994; 134: 2581-2588.
[30] Xu XF, Bjorntorp P. Effects of sex steroid hormones on differentiation of adipose precursor cells in primary culture. Exp Cell Res 1987; 173: 311-321.
[31] Ishid Y, Tertinegg I, Heersche JN. Progesterone and dexamethasone stimulate proliferation and differentiation of osteoprogenitors and progenitors for adipocytes and macrophages in cell populations derived from adult rat vertebrae. J Bone Miner Res 1996; 11: 921-930.
[32] Van Seumeren I. Weight gain and hormone replacement therapy: are women's fears justified? Maturitas 2000; 34 (suppl 1): S3-S8.
[33] Hamosh M, Hamosh P. The effect of estrogen on the lipoprotein lipase activity of rat adipose tissue. J Clin Invest 1975; 55: 1132-1135.
[34] Gray JM, Wade GN. Food intake, body weight, and adiposity in female rats: actions and interactions of progestins and antiestrogens. Am J Physiol 1981; 240: E474-E481.
[35] Gray JM, Wade GN. Cytoplasmic estrogen, but not progestin, binding sites in male rat adipose tissues. Am J Physiol 1980; 239: E237-E241.
[36] Szymczak J, Milewicz A, Thijssen JHH, Blankenstein MA, Daroszewski J. Concentration of sex steroid in adipose tissue after menopause. Steroids 1998; 63: 319-321.
13
[37] Rozenbaum H. Relationships between chemical structure and biological properties of progestogens. Am J Obstet Gynecol 1982; 142: 719-724.
[38] Lehtonen A, Gronroos M, Marniemi J, et al. Effects of high dose progestin on serum lipids and lipid metabolizing enzymes in patients with endometrial cancer. Horm Metabol Res 1985; 17: 32-34.
[39] Iverius P-H, Brunzell JD. Relationship between lipoprotein lipase activity and plasma sex steroid levels in obese women. J Clin Invest 1988; 82: 1106-1112.
[40] Price TM, O'Brien SN, Welter BH, George R, Anadjiwala J, Kilgore M. Estrogen regulation of adipose tissue lipoprotein lipase - Possible mechanism of body fat distribution. Am J Obstet Gynecol 1998; 178: 101-107.
[41] Tomita T, Yonekura T, Okada T, Hayashi E. Enhancement in cholesterol-esterase activity and lipolysis due to 17ß-estradiol treatment in rat adipose tissue. Horm Metabol Res 1984; 16: 525-528.
[42] Valette A, Meignen JM, Mercier L, Liehr JG, Boyer J. Effects of 2-fluoroestradiol on lipid metabolism in the ovariectomized rat. J Steroid Biochem 1986; 25: 575-578.
[43] Mashchak CA, Lobo RA, Dozono-Takaon R, et al. Comparison of pharmacodynamic properties of various estrogen formulations. Am J Obstet Gynecol 1982; 144: 511-518.
[44] Price TM, O'Brien SN. Determination of estrogen receptor messenger ribonucleic acid (mRNA) and cytochrome P450 aromatase mRNA levels in adipocytes and adipose stromal cells by competitive polymerase chain reaction amplification. J Clin Endocrinol Metab 1993; 77: 1041-1045.
14
[45] O'Brien SN, Welter BH, Mantzke KA, Price TM. Identification of Progesterone Receptor in Human Subcutaneous Adipose Tissue. J Clin Endocrinol Metab 1998; 83: 509-513.