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As formerly described, one of the basic functions of TIDA neurons is the
feedback regulation, which guarantees a stable low basal prolactin level.
A high prolactin level activates the TIDA neurons to synthesize DA and
to release it into the hypophyseal portal circulation. Dopamine molecules
attach to dopaminergic receptors on pituitary mammotrophs and inhibit the
adenylate cyclase system which normally activates the cell to secrete prolactin.
Decreasing prolactin secretion decreases the drive. Several factors such
as estrogens or dopaminergic antagonists are able to set this feedback
regulation at different levels of prolactin balance. In experiments on
animals it was found that tumor formation induced by estrogens is linked
with inhibition of activity TIDA system (Demarest, Riegle, Moore, 1984;
Gottschall and Meites, 1986). Also a chronic lack of DA for example with
damage of TIDA neurons in the nucleus arcuatus or lowering the secretion
from neuron terminals in ME may induce tumors of AP (Sarkar, Gottschall,
Meites, 1984). Similarly it was observed that the inhibition of TIDA system
in patients with acromegaly or hyperprolactinemia was elicited by adenoma
of the AP (van Loon, 1978). However, when experimental animals were given
dopaminergic agonists, the hyperprolactinemia was not present. The cause
of TIDA system inhibition may be in two mechanisms. The first one is estrogen-caused
neuronal degeneration of dopaminergic cells and its axons including increased
astrocytary and microglial activities in the nucleus arcuatus (Selye, Collip,
Thomson, 1935., Brawer et al, 1978). Another mechanism is indirect: the
effect of estrogens on TIDA system through prolactin (estrogens significantly
increase the secretion of prolactin). It is considered that prolactin directly
inhibits its own secretion at the pituitary level (autoregulation feedback
of prolactin, Sarkar, Gottschall, Meites, 1984); it is probably neurotoxic
for dopaminergic cells. What the primary pathogenic mechanism evoking dysfunction
in this system is is still not known.
In the brain, catecholamines and thyroid status are generally antagonistic.
Thus, thyrotropin-releasing hormone stimulates TSH, PRL, and growth hormone
secretion from pituitary adenoma cells (Ishibashi and Yamaji, 1984), whereas
DA or DA-receptor agonists have greater effects on PRL secretion in euthyroid
than in hypothyroid rats (Foord et al., 1984). Croissandeau et al. (1994)
observed significant increases of precursor of TRH, proTRH AP concentrations
in hypothyroid rats. Their data support the view that AP TSH synthesis
is regulated by thyroid hormones and that TRH might play a role in local
regulatory mechanisms within the AP on thyrotropic function. Rondeel et
al. (1988) observed that hyperthyroidism reduced hypothalamic TRH release
but was without effect on catecholamine release. Hypothyroidism did not
alter TRH release, but the release of DA increased twofold and that of
NE decreased by 20%. Hypothalamic TRH content was not affected by the thyroid
status, but DA content in the hypothalamus decreased by 25% in hypothyroid
rats. Authors on the basis of their results assumed that TRH seems to be
an important drive for normal TSH secretion by the AP, and thyroid hormones
seem to affect the hypothalamic release of catecholamines. Tyrosine hydroxylase
content or activity in the median eminence is elevated in hypothyroid rats
and there are increased DA and NE concentrations in hypophyseal portal
blood and increased release of these catecholamines into hypophyseal blood
(Nakahara et al. 1979; Reymond, Benotto, Lemarchand-Beraud, 1987; Rondeel
et al. 1988). In contrast, in thyroidectomized rats hypothalamic dopaminergic
neuronal activity is reduced (Reymond, Benotto, Lemarchand-Beraud, 1987)
and thyroidectomy prevents increased activity of tuberoinfundibular dopaminergic
neurons in oophorectomized rats (Yang and Pan, 1994). In hyperthyroid rats,
hypophyseal portal blood concentrations and release of DA and NE are normal
(Reymond, Benotto, Lemarchand-Beraud, 1987; Rondeel et al. 1988; Yang and
Pan, 1994), although increased tyrosine hydroxylase activity and catecholamine
levels in the median eminence have been reported (Yang and Pan, 1994; Wang
et al, 1994).
In recent years, attention has focussed on interactions of thyroidal
hormones with estrogens. First evidence for this interaction was revealed
by studies of Schreiber (1979) which found that thyroidal hormones play
a key role for the determination of the degree of adenohypophyseal hypertrophy
and metabolic activation. In vivo thyroidal hormones inhibit estrogen-induced
pituitary growth, hyperplasia, and nucleolar activation of PRL cells (Schreiber,
Pribyl, Rohácová, 1970; Dušková and Schreiber, 1989;
Nedvídková and Schreiber, 1992). Zhou-Li et al. (1991) and
Koga et al. (Koga, Nakao, Sato, 1992) yielded further evidence on the interaction
between estrogens and thyroidal hormones. In contrast to the results of
Schreiber (1979), Dušková and Schreiber (1989), and Nedvídková
and Schreiber (1992) they found that under in vitro conditions thyroidal
hormones as well as estrogens stimulate proliferation of anterior pituitary
cells. This contradictory effect of thyroidal hormones on the activities
of pituitary cells under in vitro conditions is not yet explained. One
possibility is that under in vitro conditions in tissue culture of cells
some regulatory factor is not present as in in vivo systems and the regulation
by thyroid hormones may be superposed to direct influence of these hormones
on the AP cells. It was found that TRH stimulated secretion activities
of lactotroph and somatotroph cells of AP, and DA and their agonists inhibited
this activity in euthyroid animals in contrast to hypothyroid animals (Foord
et al. 1984). It is also known that decreased function of thyroid is associated
with increased secretion and release of DA and NE in hypophyseal portal
blood, whereas thyrotoxic animals have the concentration unchanged (Rondeel
et al. 1988). An interesting finding, completing relation of estrogens
and thyroid hormones, is that a chronic dose of estrogens increased the
response of lactotroph cells to TRH (Terry et al. 1988). Although TRH stimulates
prolactin secretion, whether TRH is involved in regulation by thyroid hormone
of prolactin secretion remains unclear.
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