Adrenal androgen concentrations increase during infancy in male rhesus macaques (Macaca mulatta)

Abstract

Conley AJ, Plant TM, Abbott DH, Moeller BC, Stanley SD. Adrenal androgen concentrations increase during infancy in male rhesus macaques (Macaca mulatta). Am J Physiol Endocrinol Metab 301: E1229 -E1235, 2011. First published September 6, 2011 doi:10.1152/ajpendo.00200.2011.-This study investigated adrenal androgens (AA), gonadotropins, and cortisol in castrated and gonadintact male rhesus macaques from birth through infancy. Blood samples were collected longitudinally from castrated (n ϭ 6; weekly, 1-40 wk) and intact (n ϭ 4; every other week, 1-17 wk) males. Plasma concentrations of AA were determined by liquid chromatography-tandem mass spectrometry, and plasma concentrations of cortisol and gonadotropins were determined by RIA. Dehydroepiandrosterone sulfate (DHEAS) concentrations increased almost threefold (to 8 wk), dehydroepiandrosterone (DHEA) increased more than eightfold (to 11 wk), and androstenedione doubled (to 15 wk) in five castrated infant males and declined continuously thereafter. A sixth castrated male had markedly different temporal patterns and concentrations (many times more than 2 SDs from the cohort mean) of AA and gonadotropins from first sampling (3 wk) and was excluded from analysis. Cortisol increased over 16 wk but correlated poorly with DHEAS. Luteinizing and follicle-stimulating hormones increased to peaks at 3 and 7 wk, respectively. Testis-intact males exhibited similar profiles, but with earlier peaks of DHEAS (5 wk) and DHEA and androstenedione (7 wk). Peak concentrations of DHEAS were lower and those of DHEA and androstenedione were higher in intact than castrated infants. Testosterone was undetectable in castrated males and Ͼ0.5 ng/ml in intact males but was not correlated with DHEA or DHEAS. These are the first data documenting a transient increase in AA secretion during infancy in an Old World primate and are consistent with the previously documented time course of zona reticularis development that accompanies increases in androgen synthetic capacity of the adrenal. The rhesus is a promising model for androgen secretion from the human adrenal cortex. adrenarche; human; nonhuman primate; adrenal cortex; zona reticularis; dehydroepiandrosterone; dehydroepiandrosterone sulfate; castrate; prepubertal; neonate; infant; longitudinal sampling; cortisol THE ADRENAL CORTEX SYNTHESIZES the most abundant circulating steroid in the human body, dehydroepiandrosterone sulfate (DHEAS), as well as its unconjugated form (DHEA), which are collectively referred to as adrenal androgens. Although they exhibit little or no androgenic activity themselves, DHEAS and DHEA can be used as substrates for bioactive sex steroid synthesis in tissues and cells with the appropriate complement of enzymes (27). Consequently, adrenal androgen secretion remains an important source of precursors for local estrogen production when gonadal sources are absent or suppressed (28). Diseases promoted by sex steroids, such as prostate and breast cancers, are therefore more difficult to control because of adrenal DHEAS...

Adrenarche in nonhuman primates: the evidence for it and the need to redefine it

“…Earlier studies investigating adrenarche in the rhesus macaque often placed neonates, infants, and juveniles in the same group and compared them to postpubertal groups. As noted in numerous earlier reports, and as emphasized by recent longitudinal analysis (Conley et al 2011b), adrenal androgen levels during these developmental periods are highly variable, especially within the first 2 months of life. To identify a rise in circulating androgens that might help to define adrenarche requires frequent longitudinal sampling from a very early age at least in some primates and even in human development (Remer et al 2005).…”

“…Both groups experienced a prepubertal rise in circulating androgen levels, with DHEA and DHEAS peaking by 8 and 7 weeks of age respectively (Conley et al 2011b). DHEAS levels increased nearly threefold in castrates and nearly twofold in intact animals, while DHEA increased over eightfold in castrates and over tenfold in intact males (Conley et al 2011b; Fig.…”

“…Gonadectomy apparently influences adrenal androgen secretion as adrenal androgen secretion was greater in castrates than intact male rhesus (Conley et al 2011b). This is reminiscent of an induction of a recognizable, cytochrome b5-expressing ZR in gonadectomized female marmosets when none was detected in intact controls (Pattison et al 2007).…”

“…Adrenal androgen secretion and maturation of the ZR in the rhesus monkey were recently demonstrated to be complete within the first few months of life , 2009, Conley et al 2011a. Based on the results of the recent studies, it is clear that DHEA and DHEAS secretions increase (adrenarche), but only for a few weeks of neonatal life in the rhesus (Conley et al 2011b). Thus, it appears that adrenarche may well have evolved in at least some Old World primates but occupies a narrow developmental window of weeks in duration.…”

Adrenarche in bonobos (Pan paniscus): evidence from ontogenetic changes in urinary dehydroepiandrosterone-sulfate levels

“…As a consequence, adrenarche does not occur as a single, temporarily well-defined event (Pattison et al 2009). All Old World monkeys thus far investigated, including macaques and baboons, do not exhibit a distinct rise in DHEA-S before puberty (Meusy-Dessolle & Dang 1985, Crawford et al 1997, Kemnitz et al 2000, and it has been suggested that, in these taxa, fetal zone regression and adrenarche might overlap (Nguyen & Conley 2008, Conley et al 2011. The information on DHEA-S levels in plasma from two other hominoids, gorilla and orangutan, is limited, making any conclusions about the existence of adrenarche speculative (Cutler et al 1978, Collins et al 1981.…”