Female baboon adrenal zona fasciculata and zona reticularis regulatory and functional proteins decrease across the life course

Abstract

Debate exists on life-course adrenocortical zonal function trajectories. Rapid, phasic blood steroid concentration changes, such as circadian rhythms and acute stress responses, complicate quantification. To avoid pitfalls and account for life-stage changes in adrenocortical activity indices, we quantified zonae fasciculata (ZF) and reticularis (ZR) across the life-course, by immunohistochemistry of key regulatory and functional proteins. In 28 female baboon adrenals (7.5-22.1 years), we quantified 12 key proteins involved in cell metabolism, division, proliferation, steroidogenesis (including steroid acute regulatory protein, StAR), oxidative stress, and glucocorticoid and mitochondrial function. Life-course abundance of ten ZF proteins decreased with age. Cell cycle inhibitor and oxidative stress markers increased. Seven of the 12 proteins changed in the same direction for ZR and ZF. Importantly, ZF StAR decreased, while ZR StAR was unchanged. Findings indicate ZF function decreased, and less markedly ZR function, with age. Causes and aging consequences of these changes remain to be determined.

Keywords: Adrenocortical aging; Adrenocortical life-course function; Nonhuman primate; Cortisol; Glucocorticoid; Hypothalamo-pituitary-adrenal-axis.

Fig. 1

Immunostaining in the ZF for all 12 proteins at the extremes of the age range—a young age of 8.9 years and an old age of 21.3 years. Abbreviations: mechanistic target of rapamycin (mTOR); cyclin-dependent kinase 4 (CDK4); cyclin-dependent kinase 1/2 (CDK1,2); protein Ki67 (Ki67); proliferating cell nuclear antigen (PCNA); cyclin-dependent kinase inhibitor 1 (P21); steroidogenic acute regulatory protein (StAR); glucocorticoid receptor (GR); citrate synthase (CS); cyclophilin D (CPY40); ATP-synthase (ATP5A); nitrotyrosine (NT)

Fig. 2

Immunostaining in the ZR for all 12 proteins at the extremes of the age range—a young age of 8.9 years and an old age of 21.3 years. Abbreviations: mechanistic target of rapamycin (mTOR); cyclin-dependent kinase 4 (CDK4); cyclin-dependent kinase 1/2 (CDK1,2); protein Ki67 (Ki67); proliferating cell nuclear antigen (PCNA); cyclin-dependent kinase inhibitor 1 (P21); steroidogenic acute regulatory protein (StAR); glucocorticoid receptor (GR); citrate synthase (CS); cyclophilin D (CPY40); ATP-synthase (ATP5A); nitrotyrosine (NT)

Fig. 3

Percentage annual change in area of tissue stained for all 12 proteins in the adrenal ZF (blue) and ZR (red) of 28 female baboons. Abbreviations: mechanistic target of rapamycin (mTOR); cyclin-dependent kinase 4 (CDK4); cyclin-dependent kinase 1/2 (CDK1,2); protein Ki67 (Ki67); proliferating cell nuclear antigen (PCNA); cyclin-dependent kinase inhibitor 1 (P21); steroidogenic acute regulatory protein (StAR); glucocorticoid receptor (GR); citrate synthase (CS); cyclophilin D (CPY40); ATP-synthase (ATP5A); nitrotyrosine (NT)