CELLULAR MECHANISMS OF ANDROGEN ACTION IN BRAIN

Research project

Description

The hypothalamus and limbic brain play an important role in the
regulation of gonadotropin secretion and reproductive behavior in
the male. Numerous pharmacological studies have suggested a
major role for monoaminergic neurons in mediating aspects of
both of these processes. There is, however, a complex interaction
between androgens and neurotransmitters within the brain. Not
only do changes in neurotransmission affect androgen-dependent
processes, but changes in the levels of circulating testosterone
can affect some processes relating to catecholamine transmission.
This grant proposes to study these aspects of the cellular
mechanism of androgen action by determining (1) whether
monoamines affect the metabolism of androgens to active
estrogenic metabolites (aromatization) in the brain; and (2)
whether testosterone (T) or its active metabolites, in turn,
regulate the number and/or affinity of dopamine (D2) receptors in
regions of the brain relevant to behavioral and neuroendocrine
functions. To accomplish the first objective, experiments are
outlined that will measure aromatase activity and nuclear
androgen receptor concentrations under conditions where
monoamine dynamics have ben altered by agonists, antagonists,
and synthesis blockers. The second goal will be approached with
studies that will measure the binding parameters of dopamine (D2)
receptors in male rats after various endocrine manipulations that
will vary the androgen status on the animals. Pharmacologic
intervention will be used to dissect out the contribution made by
active T metabolites. Finally, studies are proposed which will
begin to localize androgen modulated catecholamine binding
within specific hypothalamic nuclei. This studies proposed herein
will lead to a better understanding of how androgens interact with
neurotransmitters to regulate neuronal functions. Moreover the
information gained should add to our knowledge to the central
components in the physiology and pathophysiology of male
reproduction and sexual development. In a larger sense, this
research has implications for our understanding of the cellular
events underlying the action of all gonadal steroids
StatusFinished
Effective start/end date7/1/876/30/93

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

Fingerprint

Androgens
Brain
Dopamine D2 Receptors
Catecholamines
Reproductive Behavior
Sexual Development
Aromatase
Organized Financing
Gonadotropins
Synaptic Transmission
Hypothalamus
Neurotransmitter Agents
Testosterone
Steroids
Pharmacology
Neurons

Keywords

  • Medicine(all)