Involvement of microtubules in lipoprotein degradation and utilization for steroidogenesis in cultured rat luteal cells
Cells isolated from superovulated rat ovaries metabolize low density lipoprotein (LDL) and high density lipoprotein (HDL) of human or rat origin and use the lipoprotein-derived cholesterol as a precursor for progesterone production. Under in vitro conditions, both lipoproteins are internalized and degraded in the lysosomes, although degradation of HDL is of lower magnitude than that of LDL. In this report we have examined the role of cellular microtubules in the internalization and degradation of human LDL and HDL in cultured rat luteal cells. The microtubule depolymerizing agents colchicine, podophyllotoxin, vinblastine, and nocodazole as well as taxol, deuterium oxide, and dimethyl sulfoxide, which are known to rapidly polymerize cellular tubulin into microtubules, were used to block the function of microtubules. When these antimicrotubule agents were included in the incubations, degradation of the apolipoproteins of (/sup 125/I)iodo-LDL and (/sup 125/I)iodo-HDL by the luteal cells was inhibited by 50-85% compared to untreated control values. Maximum inhibitory effects were observed when the cells were preincubated with the inhibitor for at least 4 h at 37 C before treatment with the labeled lipoprotein. Lipoprotein-stimulated progesterone production by luteal cells was also inhibited by 50% or more in the presence of antimicrotubule agents. However, basal and hCG-stimulated progesterone production were unaffected by these inhibitors. The binding of (/sup 125/I)iodo-LDL and (/sup 125/I)iodo-HDL to luteal cell plasma membrane receptors was not affected by the microtubule inhibitors. Although binding was unaffected and degradation was impaired in the presence of the inhibitors, there was no detectable accumulation of undegraded lipoprotein within the cells during the 24 h of study.
- OSTI ID:
- 5844483
- Journal Information:
- Endocrinology; (United States), Journal Name: Endocrinology; (United States) Vol. 6; ISSN ENDOA
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ALKALOIDS
ANIMALS
ANTIMITOTIC DRUGS
ANTIPYRETICS
AROMATICS
AZAARENES
AZOLES
BENZIMIDAZOLES
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL FUNCTIONS
BODY
CELL CONSTITUENTS
CELL CULTURES
CELL MEMBRANES
CENTRAL NERVOUS SYSTEM DEPRESSANTS
COLCHICINE
DAYS LIVING RADIOISOTOPES
DEUTERIUM
DMSO
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
FEMALE GENITALS
FUNCTIONS
GONADS
HETEROCYCLIC COMPOUNDS
HORMONES
HYDROGEN ISOTOPES
IMIDAZOLES
INDOLES
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KETONES
KINETICS
LABELLING
LIGHT NUCLEI
LIPIDS
LIPOPROTEINS
MAMMALS
MEMBRANE PROTEINS
MEMBRANES
METABOLISM
MICROTUBULES
NUCLEI
ODD-EVEN NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
OVARIES
PREGNANES
PROGESTERONE
PROTEINS
PYRROLES
RADIOISOTOPES
RATS
REACTION KINETICS
RECEPTORS
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STABLE ISOTOPES
STEROID HORMONES
STEROIDS
SULFOXIDES
TRACER TECHNIQUES
VERTEBRATES
VINBLASTINE