Immunotoxic destruction of distinct catecholaminergic neuron populations disrupts the reproductive response to glucoprivation in female rats

Endocrinology. 2003 Oct;144(10):4325-31. doi: 10.1210/en.2003-0258. Epub 2003 Jul 3.

Abstract

We tested the hypothesis that hindbrain catecholamine (norepinephrine or epinephrine) neurons, in addition to their essential role in glucoprivic feeding, are responsible for suppressing estrous cycles during chronic glucoprivation. Normally cycling female rats were given bilateral injections of the retrogradely transported ribosomal toxin, saporin, conjugated to monoclonal dopamine beta-hydroxylase antibody (DSAP) into the paraventricular nucleus (PVN) of the hypothalamus to selectively destroy norepinephrine and epinephrine neurons projecting to the PVN. Controls were injected with unconjugated saporin. After recovery, we assessed the lesion effects on estrous cyclicity under basal conditions and found that DSAP did not alter estrous cycle length. Subsequently, we examined effects of chronic 2-deoxy-d-glucose-induced glucoprivation on cycle length. After two normal 4- to 5-d cycles, rats were injected with 2-deoxy-d-glucose (200 mg/kg every 6 h for 72 h) beginning 24 h after detection of estrus. Chronic glucoprivation increased cycle length in seven of eight unconjugated saporin rats but in only one of eight DSAP rats. Immunohistochemical results confirmed loss of dopamine beta-hydroxylase immunoreactivity in PVN. Thus, hindbrain catecholamine neurons with projections to the PVN are required for inhibition of reproductive function during chronic glucose deficit but are not required for normal estrous cyclicity when metabolic fuels are in abundance.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • Catecholamines / metabolism*
  • Cell Death
  • Deoxyglucose / pharmacology
  • Dopamine beta-Hydroxylase / immunology
  • Epinephrine / metabolism
  • Estrus / drug effects*
  • Female
  • Glucose / deficiency*
  • Immunotoxins / administration & dosage
  • Immunotoxins / pharmacology*
  • Injections
  • N-Glycosyl Hydrolases / administration & dosage
  • N-Glycosyl Hydrolases / pharmacology
  • Neurons / drug effects*
  • Neurons / physiology*
  • Norepinephrine / metabolism
  • Paraventricular Hypothalamic Nucleus / physiology
  • Plant Proteins / administration & dosage
  • Plant Proteins / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Rhombencephalon / cytology
  • Rhombencephalon / physiology
  • Ribosome Inactivating Proteins, Type 1
  • Saporins
  • Time Factors

Substances

  • Antibodies, Monoclonal
  • Catecholamines
  • Immunotoxins
  • Plant Proteins
  • Ribosome Inactivating Proteins, Type 1
  • Deoxyglucose
  • Dopamine beta-Hydroxylase
  • N-Glycosyl Hydrolases
  • Saporins
  • Glucose
  • Norepinephrine
  • Epinephrine