NEUROENDOCRINOLOGY
LETTERS including Psychoneuroimmunology, Neuropsychopharmacology,
Reproductive Medicine, Chronobiology
and
Human Ethology
ISSN 0172–780X
Dehydroepiandrosterone
regulation of prolactin gene expression in the anterior pituitary
does not depend on galanin induction Gerardo
G. Piroli 1,2,3, Luciana Pietranera 1,2, Claudia
A. Grillo 1,2,3 & Alejandro F. De Nicola
1,2
Laboratorio de Bioquímica Neuroendócrina, Instituto
de Biología y Medicina Experimental, UBA-CONICET, Buenos
Aires, Argentina.
Departamento de Bioquímica Humana, Facultad de Medicina,
Universidad de Buenos Aires, Buenos Aires, Argentina.
Present address: Laboratory of Neuroendocrinology,
The Rockefeller University, New York, USA
OBJECTIVES:
The effects of dehydroepiandrosterone (DHEA) on galanin (GAL)
and prolactin (PRL) mRNA expression in the anterior pituitary
of Fischer 344 rats were studied, taking in consideration
that: (1) DHEA is an androgen with estrogenic activity on
pituitary lactotrophs; (2) estrogens induce prolactinomas
in Fischer 344 rats; and (3) GAL has been considered the main
mediator of estrogen-induced lactotroph proliferation.
DESIGN: Female rats were ovariectomized and used as controls
or treated during 2 weeks with DHEA (500 mg/kg/day or 5 mg/kg/day
or 50 mg/kg/day) or estradiol (E2, 50 mg/kg/day), as a positive
control for pituitary growth and GAL induction. GAL and PRL
mRNA expression were studied by in situ hybridization.
RESULTS: Both DHEA and E2 induced PRL mRNA synthesis. However,
DHEA neither produced pituitary enlargement nor GAL induction,
in contrast to E2.
CONCLUSIONS: Our results shows that GAL is not involved in
the estrogenic activity of DHEA on pituitary lactotrophs,
and suggest that DHEA effects are exerted directly on the
PRL gene or through another mechanism(s) not related to GAL.
ABBREVIATIONS
AND UNITS
DHEA
– dehydroepiandrosterone
PRL – prolactin
GAL – galanin
E2 – estradiol
OD – optical density
Introduction
Estrogens
increase prolactin (PRL) expression, synthesis and secretion
in the rat [1]. When given chronically, estrogens also induce
lactotroph proliferation and pituitary enlargement [2]. These
effects are enhanced in the Fischer 344 (F344) rat [3–5],
and seem to depend on the expression of the peptide galanin
(GAL), which is positively regulated by estrogens [4, 6–8].
While GAL is present at very low levels only in somatotrophs
in the ovariectomized rat [9], the increment observed in GAL
content after estrogenization is due to its expression in lactotrophs
[9, 10]. GAL released by some lactotrophs regulates the function
of the same or other lactotrophs in an autocrine/paracrine fashion
[6, 11].
The adrenal androgen dehydroepiandrosterone (DHEA) exerts estrogenic
actions at the pituitary level. Studies with adenohypophyseal
cells showed that DHEA increases PRL cell content and reduces
lactotrophs' sensitivity to the inhibitory action of dopamine,
through a direct interaction of DHEA with estrogen receptors
[12]. In vivo studies showed that DHEA increases PRL mRNA content
in pituitaries of intact or gonadectomized rats, and also diminishes
tyrosine hydroxylase expression in the arcuate nucleus, thus
decreasing the dopaminergic inhibitory input on PRL [13].
The present study was performed to test the hypothesis that
DHEA modulates PRL expression through the regulation of the
GAL gene, by virtue of its estrogenic activity. In addition,
we evaluated the possible tumorigenic action of DHEA on the
anterior pituitary of F344 rats.
