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Postnatal development of cholesterol ester hydrolase activity in the rat adrenal
Insights
Cholesterol ester hydrolase (CEH) activity does not drive corticosterone production in infant rats. CEH activity decreases as corticosterone levels rise, indicating it
Area of Science:
- Endocrinology
- Developmental Biology
- Biochemistry
Background:
- Adrenal corticosterone production is crucial for physiological responses.
- Cholesterol ester hydrolase (CEH) activity has been implicated as a rate-limiting step in corticosterone synthesis.
- Serum corticosterone levels markedly increase in infant rats starting the third postnatal week.
Purpose of the Study:
- To investigate the developmental pattern of CEH activity in infant rat adrenal glands.
- To determine if CEH activity correlates with the developmental increase in serum corticosterone.
- To assess if substrate supply limits steroidogenesis in the developing adrenal gland.
Main Methods:
- Measurement of specific and total CEH activity in rat adrenal cytosols during postnatal development.
- Quantification of serum corticosterone levels in developing and stressed infant rats.
- Measurement of cholesterol content in adrenal mitochondria.
Main Results:
- Specific CEH activity showed an inverse relationship with serum corticosterone levels during development.
- Total CEH activity did not increase in parallel with the rise in serum corticosterone.
- Adrenal CEH activity was unaffected by stress, despite increased corticosterone levels.
- Adrenal mitochondrial cholesterol content did not increase during development.
Conclusions:
- CEH activity is not the rate-determining factor for the developmental surge in basal corticosterone.
- CEH activity does not limit stress-induced corticosterone elevation in developing rats.
- Substrate supply is unlikely to be rate-limiting for steroidogenesis in the developing adrenal gland.
Abstract:
In certain circumstances the activity of cholesterol ester hydrolase (CEH) activity is believed to be rate-limiting for corticosterone production by the adrenal. The principal aim of the current study was to determine whether the activity of CEH displays a developmental increase in the infant rat which could, in part, account for the marked increase in serum corticosterone which begins at the end of the second postnatal week. The data show that the specific activity of CEH (units/mg cytosolic protein) during development is actually a mirror image of the pattern seen for serum corticosterone, i.e. CEH activities are high when serum corticosterone concentrations are low and then fall when serum corticosterone is rising. Even when total activities of CEH in the adrenal were calculated, there was no increase in parallel with the initial rise of serum corticosterone. At each age studied, stressed pups displayed significant increases of serum corticosterone; however, their CEH activities were no different from those in the non-stressed littermates. It is concluded that the activity of CEH is not the rate-determining factor for the developmental surge of basal concentrations of serum corticosterone nor for stress-induced elevation of corticosterone during the developmental period. A second aim of the current study was to address the more general question of whether steroidogenesis in the developing adrenal is limited by substrate supply. Measurement of the cholesterol content of adrenal mitochondria showed no ontogenic increase, suggesting that substrate supply, from any source, is not rate-limiting for steroidogenesis at these ages.