Thyrotropin modulates receptors for atrial natriuretic peptide on intact human thyroid cells.
Interest in the mechanism of impaired salt and water metabolism in hypothyroidism has led to growing evidence of an interaction between atrial natriuretic peptide (ANP) and the thyroid, which includes reports of direct effects of thyroid hormone on ANP synthesis and circulating ANP levels, and of the presence of specific ANP receptors in human thyroid tissue, which may act to inhibit thyroglobulin (Tg) secretion. The authors questioned whether or not thyrotropin (TSH) has a role in this interaction. They used 125I-ANP to study the effect of TSH on ANP binding to human thyroid cells in primary culture. Binding competition by increasing concentrations of unlabeled ANP in the presence or absence of TSH was assessed by Scatchard analysis. At lower temperatures of 4 degrees C or 23 degrees C, TSH had no effect either on the ANP receptor equilibrium dissociation constant (Kd) or number of binding sites. However, at 37 degrees C, bovine TSH at 1 mU/ml reduced measurable binding sites by about 50% without affecting receptor affinity (Kd = 0.2 nM). Prolonged (6 days) coincubation of TSH with thyroid cells decreased the assayable ANP receptor. The effects of TSH appear to be specific because human luteinizing hormone, follicle-stimulatory hormone, growth hormone, human chorionic gonadotropin and iodide had no effect on ANP binding. Thus, human thyroid cells possess a single class of high-affinity, specific receptors for ANP with binding activity that is temperature dependent and modulated by TSH at physiologic temperature. TSH-mediated reduction of binding at 37 degrees C but not at 4 degrees C suggests an energy-dependent process that acts possibly by activating an ANP degradative enzyme or by changing the rate of receptor internalization and subsequent degradation.
Tseng
Y C
YC
Department of Clinical Investigation, Walter Reed Army Medical Center, Washington, DC 20307-5001.
Sellitti
D F
DF
Ahmann
A J
AJ
Burman
K D
KD
D'Avis
J C
JC
Wartofsky
L
L
D009320:Atrial Natriuretic Factor / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D017461:Receptors, Atrial Natriuretic Factor; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D013696:Temperature; D013961:Thyroid Gland / Q000166:cytology / Q000378:metabolism*; D013972:Thyrotropin / Q000494:pharmacology*; D013997:Time Factors
D011956:Receptors, Cell Surface; D009320:Atrial Natriuretic Factor; D013972:Thyrotropin; D017461:Receptors, Atrial Natriuretic Factor