Free and Solvolysable Dehydroepiandrosterone and Androsterone in Blood of Mammals Under Physiological Conditions and Following Administration of Dehydroepiandrosterone

Abstract

A gas chromatographic method has been employed for the determination of dehydroepiandrosterone (D), androsterone (A), dehydroepiandrosterone sulphate (DS) and androsterone sulphate (AS) in the peripheral blood of human subjects and in various mammals under physiological conditions and after the administration of D or DS. Unconjugated D has been isolated and the resting level determined in the rat, rabbit, dog, sheep, pig and cow, while DS was detectable in the peripheral circulation of the rat, dog and pig. Unconjugated A was present in blood of the rodents and domestic ungulates studied, while the parent sulphate could be demonstrated only in rat, dog, pig and cow. The plasma of lower mammals contained D in higher (0.8\p=n-\10.9 \g=m\g/100ml), and DS, if any, in lower level (1.5\p=n-\5.7 \g=m\g/100ml) than the human plasma samples (0.1\p=n-\2.7 and 86\p=n-\308 \g=m\g/100ml, respectively). There was a more pronounced increase in D and A than in the DS and AS level in the rat and dog following administration of D. On the contrary, exogenous D hardly affected unconjugated D and appreciably enhanced the DS level in human plasma. The conclusion drawn for human subjects, that D is the metabolically active and DS the reserve hormone, does not seem to be valid for all the animals here studied. 126

Influence of Dehydroepiandrosterone on Rabbit Intraocular Pressure

“…This would provide at a first estimate, with all the inherent assumptions including any level of endogenously derived tissue DHEA, the desired concentration to achieve the proper range of the presumed active concentration at tissue sites in the eye. We used a 3% DHEA concentration but the actual values measured in the anterior chamber fluid after 2 days of two drops per day were 3-to 30-fold less (0.02 Ìg/200 Ìl, table 4) than that calculated to be needed to be functionally active [1,2,33,34]. This discrepancy may well account for low functional pharmacologic activity seen in the present experiments.…”

“…The DHEA concentration required at the site of action is estimated, from the literature [1,2,33,34], at between 1 and 10 ÌM. With this information it is helpful to calculate the drug concentration required to be delivered to the eye.…”

“…While there is literature indicating that DHEA exists in the rabbit, it has not been examined as a function of age in this species [1,2,33,34]. Young rabbits may not behave similarly to primates in regard to DHEA reaction or pharmacological response [12,33].…”

“…Dehydroepiandrosterone (DHEA), a testosterone precursor, is a major circulatory adrenal steroid that quantitatively declines asymptotically with increasing age in primates and perhaps in other species [1,2]. Attention has been drawn to the use of this compound as a potential agent for the prevention, or reduction, of age-related processes and diseases in humans.…”

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

“…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.…”