Role of carbohydrate of human chorionic gonadotropin in the mechanism of hormone action

J Biol Chem. 1975 Dec 10;250(23):9163-9.

Abstract

The role of the carbohydrate part of human chorionic gonadotropin (hCG) was investigated by measuring the ability of hCG derivatives lacking various sugar residues to bind to rat Leydig cells and stimulate them to synthesize testosterone and cyclic adenosine 3':5'-monophosphate (cyclic AMP). Whereas sequential removal of the sialic acid, galactose, N-acetylglucosamine, and mannose residues led to a progressive increase in the effective dose of the hormone required to stimulate steroidogenesis, it resulted in a marked loss in the ability of the hormone to stimulate cyclic AMP accumulation. Low doses of the glycosidase-treated hormone derivatives were additive with hCG when their ability to stimulate testosterone synthesis was analyzed. Nevertheless, the glycosidase-treated derivatives were potent inhibitors of hCG-induced cyclic AMP accumulation, suggesting that removal of the sugars did not influence binding of the hormone to the cell as much as it reduced the ability of the bound hormone to activate adenyl cyclase. This hypothesis was further supported by our finding that the hCG derivatives were highly effective inhibitors of 125I-hGC binding to the intact cells. Removal of sialic acid and galactose enhanced the inhibition, whereas removal of all the sugar residues only decreased the inhibition slightly. The degree of these effects was comparatively small. The possibility that steroidogenesis and cyclic AMP accumulation are altered independently by hCG stimulation is discussed.

PIP: The ability of human chorionic gonadotropin (HCG) derivatives, lacking various sugar residues, to bind the rat Leydig Cells and subsequently stimulate testosterone and cyclic adenosine 3',5' monophosphate (cAMP) synthesis was studied to determine the role of the carbohydrate part of HCG. The dose of HCG required to stimulate steroidogenesis progressively increased with the sequential removal of sialic acid, galactose, N-acetylglucosamine, and mannose residues. However, the ability of HCG to stimulate cAMP accumulation was decreased. The addition of low doses of glycosidase-treated hormone derivative to HCG stimulted testosterone synthesis. However, these derivatives demonstrated a potent inhibition of HCG-induced cAMP accumulation, which suggests that the absence of sugars did not affect the binding of HCG to Leydig cells as much as it impaired the ability of the bound hormone to activate adenyl cyclase. This is supported by the finding that HCG derivatives effectively inhibited the binding of iodine-125-HCG to intact cells. This inhibition was enhanced by the removal of sialic acid and galactose, though removal of all sugar residues had only a slight inhibitory effect. The independent effect of HCG on steroidogenesis and cAMP accumulation is discussed.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylglucosaminidase
  • Animals
  • Carbohydrates / analysis
  • Chorionic Gonadotropin / analysis
  • Chorionic Gonadotropin / metabolism*
  • Chorionic Gonadotropin / pharmacology
  • Galactosidases
  • Leydig Cells / drug effects
  • Leydig Cells / metabolism*
  • Male
  • Mannosidases
  • Neuraminidase
  • Rats
  • Receptors, Cell Surface*
  • Testosterone / biosynthesis

Substances

  • Carbohydrates
  • Chorionic Gonadotropin
  • Receptors, Cell Surface
  • Testosterone
  • Galactosidases
  • Mannosidases
  • Neuraminidase
  • Acetylglucosaminidase