Lipolytic activity of progesterone and synthetic progestins on rat parametrial adipocytes in vitro.
Despite the known lipogenic properties of progesterone (P) in vivo, one study had previously reported a direct in vitro lipolytic activity of P on isolated adipocytes from rat parametrial adipose tissue (Sutter-Dub et al., 1981). The aim of the present study was to further investigate this finding. Parametrial, but not retroperitoneal adipocytes, isolated from 6-week-old female rats, showed an increase in glycerol release under P stimulation. Estrone, estradiol, estriol and testosterone were inactive. At 12 weeks of age, parametrial adipocytes were bigger and failed to respond to P. P-stimulated glycerol release was concentration-related between 10(-7) M and 10(-5) M. Compared to norepinephrine, P activity displayed less potency (EC50 around 5 X 10(-7) M vs. 10(-6) M, and 4-fold vs. 2-fold maximal stimulation, respectively). Compared to P, synthetic progestins used in therapeutics (medroxyprogesterone acetate, norethindrone acetate, megestrol acetate and nomegestrol acetate) were more active at 10(-7) M but did not induce a greater response at 10(-5) M. Some 17 alpha-hydroxy and 17 alpha-acetoxy derivatives of P or 19-norprogesterone were also tested at 10(-5) M. General agreement was found between experimental lipolytic activities and known progestative agonist properties, with the exception of 19-norprogesterone, which showed a reduced lipolytic activity compared to P, in contrast with its usually higher progestative potency. The direct in vitro lipolytic activity of P was characterized as specific of age and of the parametrial adipose tissue, concentration-related, and common to synthetic progestins.
Dorai
V
V
Preclinical Research and Development Department, Laboratoires Théramex, Monaco.
Hazard
M C
MC
Paris
J
J
Delansorne
R
R
D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D005260:Female; D066298:In Vitro Techniques; D008066:Lipolysis / Q000187:drug effects*; D011374:Progesterone / Q000494:pharmacology*; D045167:Progesterone Congeners / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D013329:Structure-Activity Relationship
D045167:Progesterone Congeners; D011965:Receptors, Glucocorticoid; D011374:Progesterone