Abstract

The hydrolysis of triglycerides and cholesteryl esters stored within cells is mediated by the enzyme, hormone-sensitive lipase. In adipose tissue and heart, hormone-sensitive lipase primarily hydrolyzes stored triglycerides to free fatty acids, while in steroidogenic tissues, it principally converts cholesteryl esters to free cholesterol for steroid hormone production. To determine whether hormone-sensitive lipase is under tissue-specific, developmental regulation, the steady state levels of hormone-sensitive lipase mRNA were determined in normal rats from late fetal life through 2 years of age. Hormone-sensitive lipase mRNA levels did not appear to vary in adipose tissue from epididymal fat pads obtained from animals between 3 weeks and 2 years of age. In heart, hormone-sensitive lipase mRNA levels were lowest in the fetus increased rapidly within the first day postnatally, and then gradually increased to stable adult levels by 2 months that were 3-fold higher than observed in fetal rats. Steady state mRNA levels of hormone-sensitive lipase in the adrenals were lowest in fetal rats, increased 4-fold during the first day and peaked at levels that were 9-fold higher by the end of the first week. Thereafter, levels fell and remained 3- to 4-fold higher than at birth throughout adult life. Hormone-sensitive lipase mRNA was undetectable in testes before 4 weeks of age and increased 25-fold to stable adult levels between 4 and 12 weeks. Thus, hormone-sensitive lipase is differentially expressed and regulated in a tissue-specific fashion during development and aging.

Highlights

  • The hydrolysis of triglycerides and cholesteryl esters stored within cells is mediated by the enzyme, hormone-sensitive lipase

  • The major enzyme responsible for the mobilization of free fatty acids from adipose tissue is hormone-sensitive lipase (HSL), whose name was coined to reflect the ability of hormones such as catecholamines, ACTH, and glucagon to stimulate the activity of this intracellular neutral lipase [3]

  • The neutral cholesterol ester hydrolase activity found in adrenals, ovaries, and testes has been identified as HSL (9-ll), and, the ability of HSL to hydrolyze stored cholesteryl esters to free cholesterol for use in steroid hormone production appears to be paramount in these steroidogenic tissues [9,10,11,12,13,14]

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Summary

METHODS

Male Sprague-Dawley rats (Simenson, Gilroy, CA) were maintained according to Stanford University guidelines on ad lib rat chow and tap water with a 12 h lightldark cycle. The tissues were immediately removed, frozen in liquid nitrogen, and stored at - 8OoC prior to RNA isolation. Fetal tissues were obtained from timed-pregnant rats (Simenson). The rats were checked hourly and the start and end of delivery was noted; delivery lasted approximately 1 h and "zero-hour" was set at the end of delivery. Rats were kept with their dams until used or until weaned at 21 days. Aged animals were obtained from the vendor as 9-month-old retired breeders. They lived for 3-15 months in the Stanford University vivarium in single cages before being used

RNA isolation
Synthesis of probes
RNA quantification
Northern blot hybridization
RESULTS
Fetal Hours
DISCUSSI O N
Full Text
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