Klinische Bedeutung der Bestimmung der Bindung von Trijodthyronin an Serumproteine mittels Dextran-Gel-Filtration

Neben den bewährten älteren Verfahren zur Bestimmung des proteingebundenen127Jods und des Radiojodumsatzes hat sich die gleichzeitige Bestimmung des sog. freien und des proteingebundenen Anteils an in vitro mit Serum inkubiertem L-Trijodthyronin-131Jod mittels Dextran-Gel-Filtration klinisch zur Differentialdiagnose von Hyperthyreose und Euthyreose bewährt. Bei Ausnützung der Verdrängung von proteingebundenem L-Trijodthyronin-131Jod durch nichtmarkiertes Hormon und bei Variation der Dextran-Gel-Menge in der Säule bietet die Methode gute Differenzierungsmöglichkeiten auch für die Schilddrüsenfunktionszustände Euthyreose und Hypothyreose. Bei dem Verfahren wird der Patient nicht mit radioaktivem Jod belastet, ein für die Kinderklinik wichtiger Gesichtspunkt. Manche Störfaktoren, die den131Jodspeicherungstest und die Bestimmung des proteingebundenen Jods (PB127I) verfälschen, haben keinen Einfluß auf die mit der Dextran-Gel-Filtration untersuchten Proteinbindungsverhältnisse für L-Trijodthyronin-131Jod. So hat sich das Verfahren für die Untersuchung von Patienten mit operativ oder durch131Jodbehandlung verkleinerten Schilddrüsen, mit endokrinem Exophthalmus und in Fällen mit vorausgegangener Jodgabe, z. B. in Form von Kontrastmitteln, besonders bewährt. Mit der Bestimmung des sog. freien L-Trijodthyronin-131Jods wird ein physiologisch und pathogenetisch wichtiger Parameter der Schilddrüsenfunktion ermittelt. Die klinische Bedeutung der Bestimmung der Bindungs-und Transportverhältnisse für Trijodthyronin mittels Dextran-Gel-Filtration wird diskutiert.In addition to conventional methods of assay of protein bound iodine (PB127I) and of131iodine turnover in the thyroid, the simultaneous determination of socalled free and protein bound 1-triiodothyronine-131I, added in vitro to serum, using dextran gel filtration was found to be clinically helpful for diagnosis of euthyroidism and hyperthyroidism. Employing discharge effects of non-labelled triiodothyronine on protein bound 1-triiodothyronine-131I and varying the amount of dextran gel in the columns, the method provides reasonably good differentiation of euthyroid and hypothyroid states. No radioactive iodine is given to patients during this procedure, a fact of importance for pediatriciens. Some factors, that influence131iodine uptake or PB127I levels, do not disturb protein binding of 1-triiodothyronine-131I as determined by dextran gel filtration. The latter method was found to be especially useful for the examination of patients with surgically, or by therapy with131iodine dissected thyroid glands, with endocrine exophthalmos, and in cases of previous iodine administration (e.g. X-ray procedures). Determination of socalled free 1-triiodothyronine-131I provides information about a factor of physiological and pathogenetical significance, its clinical meaning is discussed

Effects of oestrogens on prolactin and thyrotrophin responses to TRH in women during the menstrual cycle and under oral contraceptive treatment

The effects of physiological and pharmacological variations of oestrogens on prolactin and thyrotrophin (TSH) secretion have been studied during the menstrual cycle and under oral contraceptive treatment. Ten women were tested for prolactin and TSH responses to 200 mug TRH in the early follicular (days 4-6), periovulatory (days 14-15) and luteal phases (days 22-26) of the same menstrual cycle. Circulating plasma prolactin levels did not significantly vary in the three phases, but TSH basal levels were lower in the luteal than in the follicular and periovulatory periods. The prolactin response to TRH was significantly enhanced in the periovulatory phase, while the TSH response was slightly decreased. Seven women on sequential contraceptives exhibited increased basal and TRH-induced prolactin secretion during the oestrogen treatment, with an unaltered TSH secretion throughout therapy. Treatment with combined contraceptives did not alter either basal or TRH-induced prolactin secretion in eight women, but basal TSH secretion and its response to TRH were both reduced. These data show that oestrogens may produce different regulatory effects on prolactin and TSH secretion, particularly in the pituitary sensitivity to TRH stimulation. Physiological variations of oestrogen secretion such as those observed during the menstrual cycle can likewise modify prolactin levels. These results could provide some support for a regulatory role for prolactin in the menstrual cycle

Influence of age on the control of thyrotropin secretion by thyrotropin-releasing hormone in the male rat

Alterations with age in the control of thyrotropin (TSH) secretion by thyrotropin-releasing hormone (TRH) were evaluated at the hypothalamic and pituitary levels in young (3-5 months) and old (22-24 months) male rats. In the hypothalamus, TRH was quantified in the median eminence and in the mediobasal hypothalamus; in the adenohypophysis the membrane receptors for TRH were evaluated as well as the accumulation of TRH in the gland. As for TSH, its concentration was determined in the anterior pituitary gland and in plasma. In the hypothalamus, the concentration of TRH did not differ between young and old rats in the whole mediobasal hypothalamus, but it was significantly less in the old rats at the level of the median eminence (29.9 +/- 2.8 vs. 52.2 +/- 4.3 ng/mg protein). In the adenohypophysis, the density of receptors for TRH was greater in the old than in the young rats (23.2 +/- 3.2 vs. 13.7 +/- 1.1 fmol MeTRH/mg gland)--with no change in the affinity constant--, and the amount of TRH detected was larger (10.8 +/- 1.8 vs. 2.8 +/- 0.6 pg/mg gland), illustrative of an age-related increase in TRH accumulation in the pituitary gland. The latter results are contrasting with the findings of unchanged pituitary and plasma concentrations of TSH as well as unmodified TSH response to TRH in old rats. The present data concerning TRH and the analogy with previous observations regarding dopamine in old rats are indicative of reduced neuronal activities with age at the hypothalamic level associated with impairments in the processing of the hypothalamic hormones at the pituitary level

Neuroendocrine aspects of aging: experimental data

Aging is characterized by changes in neuroendocrine/endocrine functions which are manifest in female reproductive physiology and less perceptible in other functions such as thyroid, adrenal or growth/metabolic functions. The contribution of each level of the axis - hypothalamus, adenohypophysis or peripheral tissues - is not clearly established. Functional impairments with age are recognized in the peripheral glands (gonad, thyroid, adrenal) as well as in the pituitary, but increasing evidence is accumulating for a marked contribution of the hypothalamus in the age-associated endocrine changes observed in animals and humans. In old rats, multineuronal dysfunctions are demonstrated in the hypothalamus, with a documented decline in the activity of the neurons producing dopamine and thyrotropin-releasing hormone, and to a lesser extent luteinizing hormone- and growth hormone-releasing hormones, and alterations in regulatory mechanisms of these neurons are disclosed. Moreover, impairments are observed in the processing - binding, accumulation and intracellular distribution - of hypothalamic hormones in the adenohypophysis of old rats. Taken together, these observations are supportive of the view that the neuroendocrine/endocrine changes appearing with age result from a complex balance of functional alterations occurring at each level - central and peripheral - of the axis

The secretory activity of the tuberoinfundibular dopaminergic neurons is modulated by the thyroid status in the adult rat: consequence on prolactin secretion

An influence of thyroid status on the secretory activity of hypothalamic dopaminergic neurons was observed in adult rats and its involvement in the regulation of prolactin (PRL) secretion was examined. The secretory activity of the tuberoinfundibular dopaminergic (TIDA) neurons was evaluated by measurement of dopamine (DA) biosynthesis in the neurons and DA release into hypophysial portal blood. The accumulation of DA and PRL in the adenohypophysis as well as PRL concentration in plasma were also estimated, and the various parameters were studied in thyroidectomized (TX), sham TX, TX rats treated for 7 days with thyroxine (T4; 20 micrograms/kg body weight daily) as well as in intact rats treated similarly with T4. An enhanced secretory activity of the TIDA neurons was observed in TX compared to sham TX rats, as attested by an increased synthesis of DA in the neurons, a greater concentration of DA in hypophysial portal plasma as well as an augmented accumulation of DA in the adenohypophysis. In the same animals, PRL was reduced in the adenohypophysis and in plasma, reflecting a blunted secretion of PRL in severe hypothyroidism. Treatment of TX rats with T4 for 7 days abolished all effects observed in TX rats, DA synthesis in TIDA neurons of TX rats treated with T4 being even less than in neurons of sham TX animals. A similar treatment with T4 administered to intact rats did not affect the secretory activity of the TIDA neurons nor the secretion of PRL.(ABSTRACT TRUNCATED AT 250 WORDS