Biomaterial Database

Hormonal regulation of cholinephosphate cytidylyltransferase in human fetal lung. 1993

A Sharma, and L W Gonzales, and P L Ballard

Department of Pediatrics, University of California, San Francisco 94143.

Cytidylyltransferase (CTP: cholinephosphate cytidylyltransferase, EC 2.7.7.15, CYT) is a regulatory enzyme for synthesis of pulmonary surfactant phosphatidylcholine (PC). The effects of glucocorticoid, T3, and cAMP on CYT activity were studied in explants of human fetal lung (18-22 weeks gestation) cultured for 1-6 days in serum-free medium. Dexamethasone (Dex, 10 nM) treatment for 5 days increased homogenate CYT activity (+115%, P < 0.02) when assayed in the presence of added lipid co-factor (L-alpha-phosphatidylglycerol, PG, 1.1 mM) and tended to increase activity in its absence (+77%, P = 0.12). Cytosolic activity was also significantly elevated in the presence of added co-factor (+124%, P < 0.01), but there was no effect of Dex on microsomal specific activity. Dex increased the recovery of CYT activity in the cytosolic fraction (75% vs. 43% (control) of the homogenate activity), but not in the microsomal, nuclear or mitochondrial fractions. Assayed in the presence of added co-factor, stimulation of CYT by Dex was apparent after 48 h exposure and maximal by 5-6 days exposure to < or = 30 nM concentration. T3 or agents that increase endogenous cAMP stimulated cytosolic activity by 40% and 36-74%, respectively, after 4-6 days exposure, but none produced an additive increase in the presence of Dex. We conclude that stimulation of CYT activity contributes to hormonal induction of surfactant lipids by each of these hormones. Glucocorticoids may increase the amount of CYT enzyme as well as activate the enzyme via increased synthesis of lipid co-factor.

UI	MeSH Term	Description	Entries
D008168	Lung	Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.	Lungs
D009713	Nucleotidyltransferases	A class of enzymes that transfers nucleotidyl residues. EC 2.7.7.	Nucleotidyltransferase
D011663	Pulmonary Surfactants	Substances and drugs that lower the SURFACE TENSION of the mucoid layer lining the PULMONARY ALVEOLI.	Surfactants, Pulmonary,Pulmonary Surfactant,Surfactant, Pulmonary
D003907	Dexamethasone	An anti-inflammatory 9-fluoro-glucocorticoid.	Hexadecadrol,Decaject,Decaject-L.A.,Decameth,Decaspray,Dexasone,Dexpak,Hexadrol,Maxidex,Methylfluorprednisolone,Millicorten,Oradexon,Decaject L.A.
D004789	Enzyme Activation	Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.	Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D005333	Fetus	The unborn young of a viviparous mammal, in the postembryonic period, after the major structures have been outlined. In humans, the unborn young from the end of the eighth week after CONCEPTION until BIRTH, as distinguished from the earlier EMBRYO, MAMMALIAN.	Fetal Structures,Fetal Tissue,Fetuses,Mummified Fetus,Retained Fetus,Fetal Structure,Fetal Tissues,Fetus, Mummified,Fetus, Retained,Structure, Fetal,Structures, Fetal,Tissue, Fetal,Tissues, Fetal
D005865	Gestational Age	The age of the conceptus, beginning from the time of FERTILIZATION. In clinical obstetrics, the gestational age is often estimated from the onset of the last MENSTRUATION which is about 2 weeks before OVULATION and fertilization. It is also estimated to begin from fertilization, estrus, coitus, or artificial insemination.	Embryologic Age,Fetal Maturity, Chronologic,Chronologic Fetal Maturity,Fetal Age,Maturity, Chronologic Fetal,Age, Embryologic,Age, Fetal,Age, Gestational,Ages, Embryologic,Ages, Fetal,Ages, Gestational,Embryologic Ages,Fetal Ages,Gestational Ages
D005938	Glucocorticoids	A group of CORTICOSTEROIDS that affect carbohydrate metabolism (GLUCONEOGENESIS, liver glycogen deposition, elevation of BLOOD SUGAR), inhibit ADRENOCORTICOTROPIC HORMONE secretion, and possess pronounced anti-inflammatory activity. They also play a role in fat and protein metabolism, maintenance of arterial blood pressure, alteration of the connective tissue response to injury, reduction in the number of circulating lymphocytes, and functioning of the central nervous system.	Glucocorticoid,Glucocorticoid Effect,Glucorticoid Effects,Effect, Glucocorticoid,Effects, Glucorticoid
D006728	Hormones	Chemical substances having a specific regulatory effect on the activity of a certain organ or organs. The term was originally applied to substances secreted by various ENDOCRINE GLANDS and transported in the bloodstream to the target organs. It is sometimes extended to include those substances that are not produced by the endocrine glands but that have similar effects.	Hormone,Hormone Receptor Agonists,Agonists, Hormone Receptor,Receptor Agonists, Hormone
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man