Abstract

Mammalian pregnancy is characterized by progressive hyperinsulinaemia, raised plasma lipids and increased vulnerability to ketosis after food deprivation. The present investigations were performed to assess the role of two placental steroids, oestradiol and progesterone, in the development of these changes, since plasma titres of these hormones progressively increase during human gestation. In both human subjects and adult female rats it was demonstrated that these two steroids, separately or in combination, augment plasma insulin concentration in vivo, cause hypertrophy of pancreatic islets and promote exaggerated secretion of insulin, but not glucagon, by pancreatic islets in vitro. Hypertriglyceridaemia induced by oestrogen alone or combined with progesterone was associated with increased splanchnic production of triglyceride as well as altered tissue lipoprotein lipase (EC 3.1.1.34) and circulating apoproteins that influence activity of this enzyme. The combined regimen also increased hepatic glycogen storage and suppressed gluconeogenesis in vivo in the rat while accelerating the onset of ketosis during starvation in human subjects and in the animal model. Oestradiol and progesterone appear to effect metabolic changes in nonpregnant animals and human subjects that simulate maternal adaptations to advancing gestation, including altered endocrine pancreatic function, triglyceride metabolism and metabolic fuel storage and mobilization.