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Estrogens promote adenohypophyseal enlargement and tumor transormation,
and thyroid hormones antagonize these effects, Estradiol benzoate significantly
increased anterior pituitary (AP) mass and significantly decreased AP contents
of dopamine, dihydroxyphenylalanine, dihydroxyphenylglycol and norepinephrine,
and enhanced the number of DA-2 dopamine receptors without influence on
receptor affinity compared with values in control rats. Whereas triiodothyronine
alone produced no significant effects, when administered with estradiol
benzoate, triiodothyronine blunted estradiol benzoate-induced reductions
of AP concentrations of catecholamines, increase of DA-2 dopamine receptors,
and diminished estradiol benzoate-induced increases in AP mass.
We suggest that estrogen-induced AP growth is associated with decreased
hypothalamic release of catecholamines into the portal circulation of the
AP and that treatment with thyroid hormone prevents both the estrogen-induced
growth and catecholaminergic inhibition in the AP gland. DA-2 receptor
upregulation by estradiol benzoate could reflect a compensatory response
to decreased receptor occupation. Our results help to explain why administration
of DA-2 agonist or potentially thyroid hormone can prevent pituitary hyperplasia
and hyperprolactinemia in rats treated with estrogens.
Methylene blue (MB), a new class of antioxidant drugs, inhibitor of
guanylate cyclase, administered alone significantly reduced AP mass and
partially antagonized the estrogenic effect on the AP mass given together
with estradiol benzoate. MB decreased the content of AP TSH and prolactin
in rats, raised the serum thyroxine level, and partially prevented its
reduction by carbimazole. MB also reduced the carbimazole-induced increase
in the serum TSH to the control level, i.e. it caused the resistence to
carbimazole. On the basis of preliminary results we consider that MB influence
the dopaminergic regulations.
Key words: rats, anterior pituitary, tuberoinfundibular system, dopamine
receptors, catecholamines, thyroidal hormones, estrogens, dopamine, dihydroxyphenylalanine,
dihydroxyphenylglycol, norepinephrine, methylene blue.
Abbreviations
DA = dopamine, DOPA = dihydroxyphenylalanine, DOPAC = dihydroxyphenylglycol,
NE = norepinephrine, E = epinephrine, TIDA = tuberoinfundibular system,
PRL = prolactin, TRH = thyrotropin-releasing hormone, TSH = thyrotropic
hormone, AP = anterior pituitary, T4 = thyroxine, T3 = triiodothyronine,
cAMP = cyclic adenosine monophosphate, cGMP = cyclic quanosine monophosphate,
EB = estradiol benzoate, MB = methylene blue
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