Experimentally-induced gestational androgen excess disrupts glucoregulation in rhesus monkey dams and their female offspring.
Journal - American journal of physiology. Endocrinology and metabolism
Discrete fetal androgen excess during early gestation in rhesus monkeys (Macaca mulatta) promotes endocrine antecedents of adult polycystic ovary syndrome (PCOS)-like traits in female offspring. Because developmental changes promoting such PCOS-like metabolic dysfunction remain unclear, the present study examined time-mated, gravid rhesus monkeys with female fetuses, of which nine gravid females received 15 mg of testosterone propionate (TP) subcutaneously daily from 40-80 days (first to second trimesters) of gestation (term, mean (range): 165 (155-175) days), while an additional six such females received oil vehicle injections over the same time interval. During gestation, ultrasonography quantified fetal growth measures and was used as an adjunct for fetal blood collections. At term, all fetuses were delivered by Cesarean-section for postnatal studies. Blood samples were collected from dams and infants for glucose, insulin and total free fatty acids (FFAs) determinations. TP injections transiently accelerated maternal weight gain in dams, very modestly increased head diameter of prenatally androgenized (PA) fetuses and modestly increased weight gain in infancy compared to concurrent controls. Mild- to moderate glucose intolerance, with increased area-under-the-curve circulating insulin values, occurred in TP-injected dams during an intravenous (i.v.) glucose tolerance test in the early second trimester. Moreover, reduced circulating FFA levels occurred in PA fetuses during a third trimester i.v. glucagon-tolbutamide challenge (140 days gestation), while excessive insulin sensitivity and increased insulin secretion relative to insulin sensitivity occurred in PA infants during an i.v. glucose-tolbutamide test at ~1.5 months postnatal age. Data from these studies suggest that experimentally-induced fetal androgen excess may result in transient hyperglycemic episodes in the intrauterine environment that are sufficient to induce relative increases in pancreatic function in PA infants, suggesting in this nonhuman primate model that differential programming of insulin action and secretion may precede adult metabolic dysfunction.
Reproductive skew in female common marmosets: what can proximate mechanisms tell us about ultimate causes?
Journal - Proceedings of the Royal Society B: Biological Sciences
Common marmosets are cooperatively breeding monkeys that exhibithigh reproductive skew: most subordinate females fail to reproduce,while others attempt to breed but produce very few survivinginfants. An extensive dataset on the mechanisms limiting reproductionin laboratory-housed and free-living subordinate females providesunique insights into the causes of reproductive skew. Non-breedingadult females undergo suppression of ovulation and inhibitionof sexual behaviour; however, they receive little or no aggressionor mating interference by dominants and do not exhibit behaviouralor physiological signs of stress. Breeding subordinate femalesreceive comparable amounts of aggression to non-breeding femalesbut are able to conceive, gestate and lactate normally. In groupscontaining two breeding females, however, both dominant andsubordinate breeders kill one another's infants. These findingssuggest that preconception reproductive suppression is not imposedon subordinate females by dominants, at a proximate level, butis instead self-imposed by most subordinates, consistent withrestraint models of reproductive skew. In contrast to restraintmodels, however, this self-suppression probably evolved notin response to the threat of eviction by dominant females butin response to the threat of infanticide. Thus, reproductiveskew in this species appears to be generated predominantly bysubordinate self-restraint, in a proximate sense, but ultimatelyby dominant control over subordinates' reproductive attempts.
|Keywords : ||cooperative breeding • reproductive suppression • sexual inhibition • infanticide • dominance • subordination|
Plasticity of the Zona Reticularis in the Adult Marmoset Adrenal Cortex: Voyages of Discovery in the New World.
Journal - Journal of Endocrinology
Adrenarche in humans occurs at 5-7 years old, yet the processby which DHEA biosynthesis in the adrenal ZR increases so dramaticallyremains a matter of debate. One suggestion is that increasedDHEA production by P450c17 in the ZR results from a coincidentfall in expression of 3BHSD, which would otherwise compete forpregnenolone substrate. Nonetheless, studies of human and rhesusadrenal show that cytb5 expression increases in the ZR withDHEA biosynthesis, and cloned human and rhesus P450c17 showselective increases in 17,20 lyase activity in the presenceof cytb5. The marmoset, a New World primate, expresses a fetalzone during development which regresses after birth. Adultmales, however, do not develop an obviously functional ZR, whilefemales develop a ZR in a manner that depends on their social/gonadalstatus. In all social and physiologic states, changes in marmosetZR function relate directly to changes in the expression ofcytb5. Recent cloning and expression of marmoset P450c17 alsoshows that while amino acid sequence homology is in the orderof ~85% of that found in human and rhesus sequences, and basallyase activity is low compared to rhesus, all previously describedamino acids critical to human 17,20 lyase activity are completelyconserved. Furthermore, the 17,20 lyase activity of the marmosetP450c17 clone is dramatically increased by addition of cytb5.We propose that these combined data from the marmoset modelprovide further compelling evidence that the control of ZR cytb5expression is a key determinant of ZR function.