Adrenarche: A Survey of Rodents, Domestic Animals, and Primates

Cutler, Gordon B.; Glenn, Michael L.; Bush, R. Mitchell; Hodgen, Gary D.; Graham, Charles E.; Loriaux, D. Lynn

doi:10.1210/endo-103-6-2112

Cited by 314 publications

(189 citation statements)

References 22 publications

Supporting

Mentioning

170

Contrasting

Unclassified

Order By: Relevance

“…Furthermore, no agerelated changes in plasma DHEA levels have been documented in rodents [328]. Likewise, studies by Cutler et al suggest that circulating concentrations of DHEA(S) remain low throughout life in most mammals including the guinea pig, hamster, rabbit, dog, sheep, pig, goat, horse, and cow [329].…”

Section: Rodents and Other Mammalsmentioning

confidence: 99%

Impact of Aging on Steroid Hormone Biosynthesis and Secretion

Zaidi¹

2013

TOLSJ

View full text Add to dashboard Cite

Steroid hormones are lipophilic, low-molecular weight organic compounds all of which are derived from cholesterol. They are primarily synthesized by steroidogenic glands such as gonads (ovary and testis), the adrenal gland and, during pregnancy, by the placental trophoblasts. Limited steroid synthesis also takes place in the brain. Steroid hormones are crucial for the proper functioning of the body. They mediate a wide variety of vital physiological functions, ranging from maintaining normal reproductive function and secondary sexual characteristics, to regulating virtually every metabolic process in the body. Like many age-related endocrine disorders, aging also progressively impacts the tissue-specific synthesis and secretion of steroid hormones. The goal of this review is to summarize the effects of aging on steroid hormone synthesis and secretion by the adrenal gland and gonads of both human and experimental animal models, to describe the potential involvement of excessive oxidative stress in mediating age-related alterations in steroidogenesis, and to discuss the possible underlying mechanisms involved.

show abstract

Section: Rodents and Other Mammalsmentioning

confidence: 99%

Impact of Aging on Steroid Hormone Biosynthesis and Secretion

Zaidi¹

2013

TOLSJ

View full text Add to dashboard Cite

show abstract

“…Steroidogenic enzymes could synthesize sufficient steroid to occupy the ancestral ER. Indeed, high DHEA concentrations are found in primates during different stages in their life cycle (Cutler et al, 1978;Sklar et al, 1980;Arlt et al, 2002;Rainey et al, 2002).…”

Section: A Paradox the Er And Not The Pr Is Most Ancient: What Was Tmentioning

confidence: 99%

“…Adrenarche is a unique and puzzling property of humans and chimpanzees (Cutler et al, 1978;Sklar et al, 1980;Arlt et al 2002;Rainey et al, 2002). A better understanding of adrenarche may come from studies on the physiological responses mediated by 5 steroids in protochordates and primitive vertebrates.…”

Section: Clues For Understanding Adrenarche and Neurosteroid Action?mentioning

confidence: 99%

Co-evolution of steroidogenic and steroid-inactivating enzymes and adrenal and sex steroid receptors

Baker

2004

Molecular and Cellular Endocrinology

View full text Add to dashboard Cite

Abstract. Receptors for the adrenal and sex steroids arose by a series of gene duplications from an ancestral nuclear receptor in a primitive vertebrate, at least 540 million years ago. Sequence analysis indicates many steroidogenic and steroid-inactivating enzymes, including cytochrome P450s and hydroxysteroid dehydrogenases, arose at the same time. The estrogen receptor (ER) appears to be the ancestral steroid receptor. Initially, the redundant duplicated ER had a low specificity for its new ligand. This raises the question: "How was specificity for responses to different steroids regulated early in the evolution of steroid receptors?" Selective expression of these steroid-metabolizing enzymes provided specificity for different steroid responses in primitive vertebrates. 17 -hydroxysteroid dehydrogenase-type 1 (17 -HSD-type 1) and 17 -HSD-type 2, which preferentially catalyze the reduction and oxidation at C17 of androgens and estrogens, respectively, provide an example of this mechanism. Selective expression of either 17 -HSD-type 1 or 17 -HSD-type 2 can regulate synthesis or inactivation of androgens or estrogens in specific cells.Steroids also were important in the evolution of land animals, which began about 400 million years ago.Steroidogenic and steroid-inactivating enzymes were recruited to regulate steroid-mediated responses as organ function became more complex. For example, in the kidney 11 -HSD-type 2 prevents binding of glucocorticoids to the mineralocorticoid receptor, which is crucial for aldosterone-mediated regulation of electrolyte transport in the distal tubule. We propose that 5 steroids, such as dehydroepiandrosterone and its metabolites, were the ligands for the ancestral ER. Understanding the actions of 5 steroids in amphioxus and lamprey may shed light on adrenarche and neurosteroid actions in humans.

show abstract

“…Humans show considerably higher plasma and brain tissue DHEA levels than rodents (de Peretti and Forest 1976;Fehér et al 1977;Cutler et al 1978;Corpechot et al 1981;Lanthier and Patwardhan 1986) and the compound is known to accumulate within the brain (Baulieu and Robel 1996). Given this and assuming a catabolic function of brain tissue DHEA 7a-hydroxylase, one should expect a higher 7a-hydroxylase activity in human brain tissue than in rodent brain tissue.…”

Section: Discussionmentioning

confidence: 99%

“…Humans as well as some other primates are unique among mammals as their adrenals secrete large amounts of dehydroepiandrosterone (DHEA) and its corresponding sulfate (DHEAS; Cutler et al 1978). Circulating levels of DHEA(S) decline with age.…”

mentioning

confidence: 99%

Characterization of the dehydroepiandrosterone (DHEA) metabolism via oxysterol 7α‐hydroxylase and 17‐ketosteroid reductase activity in the human brain

Steckelbroeck¹,

Watzka²,

Lütjohann³

et al. 2002

Journal of Neurochemistry

View full text Add to dashboard Cite

Dehydroepiandrosterone and its sulphate are important factors for vitality, development and functions of the CNS. They were found to be subjects to a series of enzyme-mediated conversions within the rodent CNS. In the present study, we were able to demonstrate for the first time that membraneassociated dehydroepiandrosterone 7a-hydroxylase activity occurs within the human brain. The cytochrome P450 enzyme demonstrated a sharp pH optimum between 7.5 and 8.0 and a mean K M value of 5.4 lM, corresponding with the presence of the oxysterol 7a-hydroxylase CYP7B1. Real-time RT-PCR analysis verified high levels of CYP7B1 mRNA expression in the human CNS. The additionally observed conversion of dehydroepiandrosterone via cytosolic 17b-hydroxysteroid dehydrogenase activity could be ascribed to the activity of an enzyme with a broad pH optimum and an undetectably high K M value. Subsequent experiments with cerebral neocortex and subcortical white matter specimens revealed that 7a-hydroxylase activity is significantly higher in the cerebral neocortex than in the subcortical white matter (p < 0.0005), whereas in the subcortical white matter, 17b-hydroxysteroid dehydrogenase activity is significantly higher than in the cerebral neocortex (p < 0.0005). No sex differences were observed. In conclusion, the high levels of CYP7B1 mRNA in brain tissue as well as in a variety of other tissues in combination with the ubiquitous presence of 7a-hydroxylase activity in the human temporal lobe led us to assume a neuroprotective function of the enzyme such as regulation of the immune response or counteracting the deleterious effects of neurotoxic glucocorticoids, rather than a distinct brain specific function such as neurostimulation or neuromodulation.

show abstract

Adrenarche: A Survey of Rodents, Domestic Animals, and Primates

Cited by 314 publications

References 22 publications

Impact of Aging on Steroid Hormone Biosynthesis and Secretion

Impact of Aging on Steroid Hormone Biosynthesis and Secretion

Co-evolution of steroidogenic and steroid-inactivating enzymes and adrenal and sex steroid receptors

Characterization of the dehydroepiandrosterone (DHEA) metabolism via oxysterol 7α‐hydroxylase and 17‐ketosteroid reductase activity in the human brain

Contact Info

Product

Resources

About