Interleukin-1 alpha as a potent inhibitor of gonadotropin action in porcine Leydig cells: site(s) of action

Biol Reprod. 1992 Jun;46(6):1119-26. doi: 10.1095/biolreprod46.6.1119.

Abstract

The effects of interleukin on testicular steroidogenesis have been studied in several laboratories, most often by using cultured rat Leydig cells. Several reports have indicated that interleukin-1 beta (IL-1 beta), but not interleukin-1 alpha (IL-1 alpha), exert a potent effect on gonadotropin action in rat Leydig cells. By using cultured porcine Leydig cells as a model, we found that IL-1 alpha (and to a lesser extent IL-1 beta), contrary to previous reports, is a potent inhibitor of LH/hCG steroidogenic action; and we further localized the steroidogenic biochemical step(s) affected by IL-1 alpha. IL-1 alpha inhibited hCG-induced testosterone secretion (about 67%) in a dose- and time-dependent manner. Half maximal and maximal effects were obtained with 4 U/ml (approximately 0.4 ng/ml, 0.3 x 10(-10) M) and 20 U/ml (approximately 2 ng/ml, 1.4 x 10(-10) M) of IL-1 alpha, respectively. The inhibitory effect of IL-1 alpha on gonadotropin action was detected at 6 h and was maximal after 24 h of treatment with the cytokine. The IL-1 alpha inhibitory effect was more potent than that of IL-1 beta: the maximal inhibitory effect of IL-1 beta was obtained with 400 U/ml. Subsequent investigations indicated that IL-1 alpha inhibited different biochemical steps involved in gonadotropin-induced testicular steroidogenesis. In this context, although IL-1 alpha appears to inhibit Leydig cell membrane functions (through a decrease in LH/hCG binding and gonadotropin-induced cAMP production), the antigonadotropin action of the cytokine is probably exerted predominantly at a step(s) located beyond cAMP formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Bromo Cyclic Adenosine Monophosphate / pharmacology
  • Animals
  • Cells, Cultured
  • Chorionic Gonadotropin / pharmacology*
  • Cyclic AMP / physiology
  • Epidermal Growth Factor / pharmacology
  • Hydroxycholesterols / pharmacology
  • Interleukin-1 / pharmacology*
  • Leydig Cells / drug effects
  • Leydig Cells / metabolism*
  • Luteinizing Hormone / pharmacology*
  • Male
  • Swine
  • Testosterone / biosynthesis*
  • Testosterone / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Chorionic Gonadotropin
  • Hydroxycholesterols
  • Interleukin-1
  • Tumor Necrosis Factor-alpha
  • 22-hydroxycholesterol
  • 8-Bromo Cyclic Adenosine Monophosphate
  • Testosterone
  • Epidermal Growth Factor
  • Luteinizing Hormone
  • Cyclic AMP