Pattern of maternal circulating CRH in laboratory-housed squirrel and owl monkeys

Abstract

The anthropoid primate placenta appears to be unique in producing corticotropin-releasing hormone (CRH). Placental CRH is involved in an endocrine circuit key to the production of estrogens during pregnancy. CRH induces cortisol production by the maternal and fetal adrenal glands, leading to further placental CRH production. CRH also stimulates the fetal adrenal glands to produce dehydroepiandrostendione sulfate (DHEAS), which the placenta converts into estrogens. There are at least two patterns of maternal circulating CRH across gestation among anthropoids. Monkeys examined to date (Papio and Callithrix) have an early-to-mid gestational peak of circulating CRH, followed by a steady decline to a plateau level, with a possible rise near parturition. In contrast, humans and great apes have an exponential rise in circulating CRH peaking at parturition. To further document and compare patterns of maternal circulating CRH in anthropoid primates, we collected monthly blood samples from 14 squirrel monkeys (Saimiri boliviensis) and ten owl monkeys (Aotus nancymaae) during pregnancy. CRH immunoreactivity was measured from extracted plasma by using solid-phase radioimmunoassay. Both squirrel and owl monkeys displayed a mid-gestational peak in circulating CRH: days 45-65 of the 152-day gestation for squirrel monkeys (mean±SEM CRH=2,694±276 pg/ml) and days 60-80 of the 133-day gestation for owl monkeys (9,871±974 pg/ml). In squirrel monkeys, circulating CRH declined to 36% of mean peak value by 2 weeks before parturition and then appeared to increase; the best model for circulating CRH over gestation in squirrel monkeys was a cubic function, similar to previous results for baboons and marmosets. In owl monkeys, circulating CRH appeared to reach plateau with no subsequent significant decline approaching parturition, although a cubic function was the best fit. This study provides additional evidence for a mid-gestational peak of maternal circulating CRH in ancestral anthropoids that has been lost in the hominoid lineage.

Figure 1

Simple phylogenetic representation of species tested for presence/absence of maternal circulating CRH during pregnancy. + indicates CRH detected; − indicates CRH not detected; ? means no species in these taxa have been tested. Data from Power and Schulkin, 2006.

Figure 2

Maternal circulating CRH in pregnant squirrel monkeys; open circles identify samples from live births and filled circles identify samples from term stillbirths. The best fit curve was a cubic function.

Figure 3

Maternal circulating CRH in pregnant owl monkeys. Open circles identify samples from before or after gestation; closed circles identify samples from during gestation. Vertical dashed lines indicate the beginning and end of gestation. Excluding the four highest values during gestation and all values before day 20 of gestation resulted in the best fit curve for maternal circulating CRH across gestation being a cubic function (shown).

Figure 4

The patterns of maternal circulating CRH across pregnancy in (A) baboons (Papio hamydryas), data from Goland et al., 1992; and (B) common marmosets (Callithrix jacchus), data from Power et al., 2006. The arrow indicates a value from a triplet pregnancy that subsequently aborted.