Effects of toxic levels of lead on gene regulation in the male axis

Increase in messenger ribonucleic acids and intracellular stores of gonadotrophs within the central nervous system

D. Klein, Yu-Jui Yvonne Wan, S. Kamyab, H. Okuda, R. Z. Sokol

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49 Citations (Scopus)

Abstract

Lead is a male reproductive toxicant. Lead exposure results in a general suppression of the hypothalamic-pituitary-testicular (HPT) axis in male rats. The mechanism(s) for this disruption by lead is unknown. Toxic lead levels seem to disrupt central nervous system (CNS) control of the HPT system, resulting in a decrease in serum testosterone levels and sperm concentrations. A study designed to elucidate the mechanisms accounting for the disruption of the normal function of the male axis by toxic lead levels at the molecular level demonstrated a 2-3-fold enhancement of mRNA levels of GnRH and the tropic hormone LH. A 3-fold increase of intracellular stores of LH was also found. Because mRNA levels of LH and GnRH and pituitary levels of stored LH are proportional to blood levels of lead, we hypothesize that lead interferes with the normal release of tropic hormones and disrupts hormonal feedback mechanisms. The observed pleiotropic effects of lead upon the male axis and other systems may be explained by simple and unique competition by lead with normal metal ion binding sites that govern genetic control of specific genes.

Original languageEnglish (US)
Pages (from-to)802-811
Number of pages10
JournalBiology of Reproduction
Volume50
Issue number4
StatePublished - 1994

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Gonadotrophs
Poisons
Central Nervous System
RNA
Genes
Gonadotropin-Releasing Hormone
Hormones
Lead
Messenger RNA
Testosterone
Spermatozoa
Metals
Binding Sites
Ions

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Embryology

Cite this

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title = "Effects of toxic levels of lead on gene regulation in the male axis: Increase in messenger ribonucleic acids and intracellular stores of gonadotrophs within the central nervous system",
abstract = "Lead is a male reproductive toxicant. Lead exposure results in a general suppression of the hypothalamic-pituitary-testicular (HPT) axis in male rats. The mechanism(s) for this disruption by lead is unknown. Toxic lead levels seem to disrupt central nervous system (CNS) control of the HPT system, resulting in a decrease in serum testosterone levels and sperm concentrations. A study designed to elucidate the mechanisms accounting for the disruption of the normal function of the male axis by toxic lead levels at the molecular level demonstrated a 2-3-fold enhancement of mRNA levels of GnRH and the tropic hormone LH. A 3-fold increase of intracellular stores of LH was also found. Because mRNA levels of LH and GnRH and pituitary levels of stored LH are proportional to blood levels of lead, we hypothesize that lead interferes with the normal release of tropic hormones and disrupts hormonal feedback mechanisms. The observed pleiotropic effects of lead upon the male axis and other systems may be explained by simple and unique competition by lead with normal metal ion binding sites that govern genetic control of specific genes.",
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T2 - Increase in messenger ribonucleic acids and intracellular stores of gonadotrophs within the central nervous system

AU - Klein, D.

AU - Wan, Yu-Jui Yvonne

AU - Kamyab, S.

AU - Okuda, H.

AU - Sokol, R. Z.

PY - 1994

Y1 - 1994

N2 - Lead is a male reproductive toxicant. Lead exposure results in a general suppression of the hypothalamic-pituitary-testicular (HPT) axis in male rats. The mechanism(s) for this disruption by lead is unknown. Toxic lead levels seem to disrupt central nervous system (CNS) control of the HPT system, resulting in a decrease in serum testosterone levels and sperm concentrations. A study designed to elucidate the mechanisms accounting for the disruption of the normal function of the male axis by toxic lead levels at the molecular level demonstrated a 2-3-fold enhancement of mRNA levels of GnRH and the tropic hormone LH. A 3-fold increase of intracellular stores of LH was also found. Because mRNA levels of LH and GnRH and pituitary levels of stored LH are proportional to blood levels of lead, we hypothesize that lead interferes with the normal release of tropic hormones and disrupts hormonal feedback mechanisms. The observed pleiotropic effects of lead upon the male axis and other systems may be explained by simple and unique competition by lead with normal metal ion binding sites that govern genetic control of specific genes.

AB - Lead is a male reproductive toxicant. Lead exposure results in a general suppression of the hypothalamic-pituitary-testicular (HPT) axis in male rats. The mechanism(s) for this disruption by lead is unknown. Toxic lead levels seem to disrupt central nervous system (CNS) control of the HPT system, resulting in a decrease in serum testosterone levels and sperm concentrations. A study designed to elucidate the mechanisms accounting for the disruption of the normal function of the male axis by toxic lead levels at the molecular level demonstrated a 2-3-fold enhancement of mRNA levels of GnRH and the tropic hormone LH. A 3-fold increase of intracellular stores of LH was also found. Because mRNA levels of LH and GnRH and pituitary levels of stored LH are proportional to blood levels of lead, we hypothesize that lead interferes with the normal release of tropic hormones and disrupts hormonal feedback mechanisms. The observed pleiotropic effects of lead upon the male axis and other systems may be explained by simple and unique competition by lead with normal metal ion binding sites that govern genetic control of specific genes.

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