Role of GABA in the control of thyrotropin secretion in the rat.

Various doses of GABA from 0.25 to 5 mumol injected into the third ventricle decrease serum TSH rapidly. The same effect was observed with GABOB (10 mumol), the hydroxylated form of GABA. The inhibitory effect of both of these drugs was prevented by picrotoxin injection (1 microgram). Peripheral injection of GABAergic drugs such as GABOB or AOAA also decreased serum TSH. In vitro, the addition of GABA (from 6.7 . 10(-6) to 6.7 . 10(-4) M) to the incubation medium of hemi-anterior pituitary did not modify the liberation of TSH. To test the physiological role of GABA in the regulation of thyrotropin function the circadian TSH rhythm was used as a model. Both GABAergic inhibitors, picrotoxin (10 microgram/kg b.w.) as well as semicarbazide (150 mg/kg b.w.), induced an increase of the low basal nocturnal level of TSH (centered on the 02.00 h time point) without altering the diurnal peak of TSH. We conclude that GABA has an inhibitory effect on central thyrotropin control via an inhibition of TRH release from the hypothalamus and might be, at least partly, responsible for the low nocturnal levels of serum TSH observed during the circadian physiological rhythm.

TRH and LH-RH distribution in discrete nuclei of the human hypothalamus: evidence for a left prominence of TRH.

Thyrotropin-releasing hormone (TRH) and luteinizing hormone-releasing hormone (LH-RH) have been measured by radioimmunoassay in individual human hypothalamic nuclei. A significant lateralization has been found for TRH in the ventromedial, dorsal and paraventricular nuclei, with higher concentration in the left side. In contrast LH-RH values did not differ between the left and the right side. This finding represents an additional example of cerebral specialization and the first report of lateralized peptide distribution in the human hypothalamus.

In vitro effects of endogenous opiate peptides on thyrotropin function: inhibition of thyrotropin-releasing hormone release and absence of effect on thyrotropin release.

Thyrotropin-releasing hormone (TRH) or thyroid-stimulating hormone (TSH) was measured by radioimmunoassay in the incubation medium of rat hypothalami or anterior pituitary halves, respectively. We studied the effect of opioid peptide addition (10(-8) to 10(-6) M) on TRH or TSH release. alpha- or beta-Endorphin decreased TRH release in a dose-dependent manner while only 10(-6) M Leu- or Met-enkephalin decreased TRH release. These inhibitory effects were prevented by addition of naloxone (10(-5) M). In the dose range used none of the opioid peptides modified TSH release. These results indicate that opioid peptides may play a role in the regulation of thyrotropin secretion via a hypothalamic action on TRH release.

[Topographic and chemical study of the GABA synthetizing enzyme in Parkinsonian syndromes]. / Etude topographique et chimique de l'enzyme de synthèse du GABA dans les syndromes parkinsoniens.

After a classical neuropathological study assessing the diagnosis, the activity of the GABA synthetizing enzyme, glutamate decarboxylase (GAD), was assayed in 6 brain areas, in 8 cases of Parkinson's disease, 2 cases of idiopathic orthostatic hypotension and 9 control cases carefully matched. The activity of GAD is not impaired, as classically believed, in parkinsonian brains, particularly in substantia nigra and pallidum. This preservation would indicate the absence of lesion of GABAergic neurones in Parkinson's disease. In the cases of other Parkinsonian syndromes, the number of cases studied is too limited to allow any generality; but they are, however reported because of their rarity.

Zinc may play a role in the regulation of thyrotropin function.

We studied the in vitro and in vivo influence of physiologically relevant zinc concentrations on the thyrotropin function both at the pituitary and hypothalamic level. Zinc gluconate (Zn Glu) concentrations from 5 to 100 microM decreased basal TSH release from anterior pituitary gland in vitro, but did not affect TSH-stimulated release by TRH, cAMP or high K+ concentrations. Zn Glu altered neither the basal nor stimulated production of TRH by hypothalami in vitro. In vivo brain third ventricle injection of Zn Glu decreased serum TSH 30-60 min after injection. The ability of physiological concentrations of zinc to influence TSH secretion both in vitro and in vivo suggest that this trace element might be involved in the regulation of thyrotropin function.

Postnatal development of TRH and TSH rhythms in the rat.

We previously observed that under a 12-hour light/12-hour dark schedule (lights off at 19.00 h), adult male Sprague-Dawley rats showed a circadian rhythm for serum thyroid-stimulating hormone (TSH) with a zenith near midday. In the present work, the ontogenesis of serum TSH rhythm was determined as well as pituitary TSH variations. In addition, hypothalamic and blood TRH were measured in these rats aged 15, 25, 40 and 70 days when sacrificed. As from the first age studied (15 days), a hypothalamic thyrotropin-releasing hormone (TRH) circadian rhythm was present. The mesor and the amplitude of this hypothalamic TRH rhythm increased while the rats were growing up, in contrast with the decrease observed for these parameters as far as blood TRH circadian rhythm is concerned. The time of the acrophase moved from 17.32 h in the 15-day-old rats to 13.57 h in the 70-day-old rats, being constantly in phase opposition with the blood TRH acrophase. The low amplitude pituitary TSH circadian rhythm detected in the young rat disappeared in the adult while, in contrast, the serum TSH rhythm became consistent to reach the well-characterized circadian midday peak in the 70-day-old rats.

Thyroid-hypophyso-hypothalamic axis of the genetically hypoprolactinemic rats (IPL nude rats).

In order to evaluate thyrotropin function in the genetically hypoprolactinemic rat, (IPL nude), we measured by radioimmunoassay TRH hypothalamic content, pituitary TSH content and serum TSH, T3, T4, both in IPL nude and control rats at various times over the 24-hour period. Compared to normal rats, the hypothalamic TRH content in the IPL nude rat showed similar variations during the day, whereas a slight increase was observed during the night characterized by a significant difference at 20.00 h. Pituitary weight and TSH content were doubled in IPL nude rats; however, when expressed as micrograms TSH/micrograms protein or DNA, a significant increase was found only at 17.00 and 20.00 h. Serum TSH and total serum T3, T4 depicted similar variations although they were minute but nonetheless significant modifications, i.e. an increase of TSH at 17.00 and 23.00 h and a decrease of T4 at 11.00 h. However, only FT4 concentrations (and not-FT3) were slightly but significantly decreased in IPL rats over the experimental times. In conclusion, the slight increase in hypothalamic TRH and pituitary TSH contents and the absence of main associated variations of serum TSH, T3 and T4 do not lend support to the hypothesis that TRH could be the cause of the hypoprolactinemia of these rats. On the contrary, the observed thyrotropin axis variations might be rather interpreted as the consequence of it.

Disappearance of hypothalamic TRH asymmetry in suicide patients.

The aim of the present study was to investigate the functional and/or pathological significance of the hemispherical lateralization of TRH using radioimmunoassay to determine the TRH concentration of nuclei and areas within the hypothalamus of suicide patients, with matching measurement being carried out on control subjects. In suicide patients, we found no significant difference in TRH concentration between the left and right intrahypothalamic structures, while the group used as control subjects (see Borson-Chazot, 1986) showed a significant left side predominance in the ventromedial nucleus, paraventricular nucleus and area dorsalis. As regards the TRH concentration in the right intrahypothalamic structures, no significant difference was found between the suicide patients and the control subjects. The absence of the left TRH predominance for the three intra-hypothalamic structures in question may be of pathological significance.