Multiple expressions of the activity of guanine nucleotide regulatory protein in human thyroid adenylate cyclase

Abstract

Adenylate cyclase (ATP pyrophosphate-lyase, EC 4.6.1.1) in plasma membranes from human thyroid was highly responsive to thyrotropin. Pretreatment of thyroid plasma membranes with 5'-guanylylimidodiphosphate (Gpp(NH)p) in the presence of Mg 2+ led to a temperature-dependent activation, which was seen neither in the absence of Mg 2+ nor at 4°C. By contrast, thyrotropin bound to its receptors regardless of the temperature and produced its maximal effect after 2 min of preincubation in the absence or presence of Mg 2+. Furthermore, activation was seen after treatment with thyrotropin and Gpp(NH)p even carried out in the absence of Mg 2+ or at 4°C. However, the full activation by Gpp(NH)p required Mg 2+, hormone, and elevated temperature. These observations suggest that there appears to be two types of nucleotide interaction responsible for the Gpp(NH)p activation in human thyroid membrane; one type seen in the absence of hormone may represent the system uncoupled from hormone receptor, while the fully coupled hormone-sensitive adenylate cyclase accounts for the second type of interaction which requires the presence of hormone.