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Development of pituitary-adrenal endocrine function in the marmoset monkey: infant hypercortisolism is the norm
Christopher R Pryce1, Rupert Palme, Joram Feldon
1Behavioural Neurobiology Laboratory, Swiss Federal Institute of Technology Zurich, CH-8603 Schwerzenbach, Switzerland. pryce@toxi.biol.ethz.ch
Insights
Early life stress impacts adult stress systems. In marmosets, elevated neonatal cortisol and ACTH, unlike in rats, suggest a unique primate model for studying early life stress effects.
Area of Science:
- Endocrinology
- Neuroscience
- Primate Models
Background:
- Early life stress alters hypothalamic-pituitary-adrenal (HPA) system function in adulthood.
- Rat models show low basal HPA activity and stress hyporesponsiveness during infancy.
- Infant exposure to atypical glucocorticoid levels can chronically alter HPA function.
Purpose of the Study:
- To investigate changes in pituitary-adrenal function during the early development of the common marmoset.
- To compare primate HPA ontogeny with existing rat models.
- To assess the implications of early life hypercorticoidism in a primate model.
Main Methods:
- Measured plasma ACTH and cortisol levels across various life stages from birth to adulthood in marmosets.
- Assessed cerebrospinal fluid cortisol levels in infants, juveniles, and subadults.
- Evaluated ACTH and cortisol stress responses and recovery in infant and subadult marmosets.
Main Results:
- Neonatal and 4-week-old marmosets exhibited elevated basal ACTH and cortisol levels compared to older stages.
- Neonates lacked circadian cortisol rhythm, showing consistently high levels and larger adrenal glands.
- Infants displayed similar peak stress responses but retarded cortisol recovery post-stress compared to subadults.
Conclusions:
- The common marmoset displays a distinct HPA ontogeny with elevated neonatal cortisol, differing from the rat model.
- This primate model offers a valuable tool for studying the long-term effects of early life hypercorticoidism.
- Findings contribute to understanding primate stress system development and its biomedical implications.
Abstract:
Early life stress, involving activation of the hypothalamic-pituitary-adrenal (HPA) system, is associated with altered functioning of stress-related systems in adulthood. In the rat, postnatal development is characterized by low basal HPA activity and stress hyporesponsiveness, and infant exposure to atypical glucocorticoid levels leads to chronic alteration of HPA function and HPA-dependent peripheral and central processes. There have been few studies of primate HPA ontogeny, and here we report a study of changes in pituitary-adrenal function between birth and adulthood in the common marmoset monkey. In this simian primate, basal plasma ACTH and cortisol levels were actually elevated in neonates (ACTH, 141 +/- 28 pg/ml; cortisol, 1903 +/- 326 microg/dl) and wk 4 infants (ACTH, 114 +/- 9 pg/ml; cortisol, 290 +/- 8 microg/dl) relative to month 2 infants, juveniles (month 6), subadults (month 12), and adults (>2 yr; ACTH, 37 +/- 4 to 61 +/- 8 pg/ml; cortisol, 101 +/- 2 to 195 +/- 4 microg/dl). In contrast to older life stages, neonates lacked circadian change in their plasma cortisol levels, and this state of consistently high cortisol was associated with large adrenal glands in addition to high ACTH levels. Cerebrospinal fluid cortisol levels were, in accord with plasma levels, higher in wk 4 infants than in juveniles and subadults. In terms of stress response, month 2 infants demonstrated ACTH and cortisol peak stress responses similar to those at older life stages (infant stress cortisol, 185 +/- 36% of basal; subadult stress cortisol, 174 +/- 6% of basal); whereas infant ACTH recovery was also similar to that in older subjects, their cortisol poststress recovery was retarded. This primate, it is proposed, provides an excellent complementary model in which to test hypotheses derived from the rat model relating to HPA system ontogeny and the chronic effects and biomedical implications of hypercorticoidism during early life.