Effect of rhGH on the synthesis and secretion of VLDL to lymph and plasma from the intestine of the female rat.
The intravenous administration of rhGH (recombinant human Growth Hormone) to fasting female rats causes an increase in the rate of synthesis and secretion of VLDL (very low density lipoproteins). This phenomenon has three striking characteristics: (1) the demonstration of an unexpected lipogenic effect of rhGH, (2) its rapid occurrence after intravenous injection of the hormone and (3) the apparent dependence on the levels of circulating estrogens, as deduced by the lack of effect of rhGH on males and castrated females. The target tissue for the lipogenic effect was traced to the intestine by means of perfusion experiments of isolated duodenal loops. Impairment of liver blood supply discarded this tissue as the source of VLDL induced by rhGH. After a single dose of rhGH (T(1/2)=16min), the increase in plasma TAG (triacylglycerides) levels followed a positive exponential course that lasted ca. 3h. The same phenomenon (with no significant differences in kinetic parameters) was observed in three other experimental circumstances: fasting intact virgin female rats with impaired hepatic circulation, perfusion of isolated duodenum and sampling of mesenteric lymph. It is assumed that rhGH stimulates the synthesis of TAG and VLDL by the physiological mechanisms already present in enterocytes. Because increased plasma levels of VLDL and GH have been demonstrated in the last week of rat pregnancy, we believe that the reported phenomenon has physiological implications, hypothetically associated with fetal lung maturation. As an hypothesis, we suggest that the effect of growth hormone (of pituitary or placental origin) on the synthesis and secretion of VLDL by enterocytes uses a nongenomic pathway.
Lioi
Susana A
SA
Laboratorio de Biología Osea, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Santa Fe 3100, 2000 Rosario, Argentina. salioi@yahoo.com
Rigalli
Alfredo
A
Puche
Rodolfo C
RC
D000818:Animals; D015243:Cholesterol, VLDL / Q000096:biosynthesis* / Q000378:metabolism* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D019382:Human Growth Hormone / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects*; D008196:Lymph / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D010052:Ovariectomy; D010949:Plasma / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D014280:Triglycerides / Q000493:pharmacokinetics
D015243:Cholesterol, VLDL; D004967:Estrogens; D011994:Recombinant Proteins; D014280:Triglycerides; D019382:Human Growth Hormone