Thyrotropic Function Research Articles

Serotonin concentration in the hypothalamus during changes in pituitary thyrotropic function

The serotonin concentration in the hypothalamus was determined in sexually mature male rabbits during changes in pituitary thyrotropic function. No clear parallel was observed between the intensity of the pituitary thyrotropic function and the hypothalamic serotonin concentration. Stimulation of pituitary thyrotropic function by injection of 6-methylthiouracil or by partial thyroidectomy was accompanied by an increase in the serotonin concentration, whereas during aseptic inflammation in the thyroid gland or after a combination of removal of the superior cervical sympathetic ganglia and administration of chlorpromazine, the increase in thyrotropic function occurred without any significant changes in the hypothalamic serotonin concentration.

Adrenal Insufficiency Secondary to Hypothalamic Corticotropin Releasing Factor (CRF) Insufficiency with Hyperpigmentation: A Case Report

Partial adrenocortical insufficiency as a result of an insufficiency of the hypothalamic corticotropin releasing factor (CRF) was demonstrated in a 53-year-old female patient. Somatotropic, gonadotropic and thyreotropic functions of the pituitary gland were shown to be normal by a simultaneous pituitary stimulation test. This held true especially for the adrenocorticotrophic function: administration of lysine-vasopressin induced a normal rise in immunoreactive plasma-ACTH. Thus, a pituitary defect as a primary cause of the disease could be excluded and evidence was provided that there was a lack in hypothalamic stimulae absence of elevated ACTH levels hyperpigmentation of the skin existed. Possible explanations are discussed.

Recovery of Pituitary Thyrotropic Function after Withdrawal of Prolonged Thyroid-Suppression Therapy

The pattern of thyrotropin secretion was analyzed in seven euthyroid women, before and after withdrawal of long-term thyroid hormone, by serial measurements of thyroid 131l uptake, serum thyroxine, tri-iodothyronine, and thyrotropin concentrations, and the response to thyrotropin-releasing hormone. During exogenous hormone administration, 131l uptake was suppressed, and serum thyrotropin concentrations before and after administration of thyrotropin-releasing hormone were undetectable. After withdrawal of exogenous hormone, thyrotropin secretory function was transiently impaired, as indicated by undetectable basal thyrotropin concentrations together with absence of response to thyrotropin-releasing hormone, and subsequently by normal values of basal thyrotropin concentration and normal responses to releasing hormone while serum thyroxine and tri-iodothyronine concentrations were subnormal. Decreased thyrotropin reserve persisted for two to five weeks. Detectable values of serum thyrotropin (less than 1.2 muU per milliliter) and a normal 131l uptake usually occurred concurrently in two to three weeks. Serum thyroxine concentration returned to normal at least four weeks after hormone withdrawal.

Plasma Immunoreactive T3, TSH and ACTH Before and After Provocative Tests in Idiopathic Hypopituitary Dwarfism

The somatotropic, thyrotropic and corticotropic functions were investigated in 8 patients with idiopathic pituitary dwarfism. Particularly interesting were the results obtained from studies of the thyrotropic function. In the absence of clinical and conventional laboratory indices of hypothyroidism, measurement of plasma immunoreactive T3 and TSH before and after iv administration of 400 μg of TRH suggested the presence of borderline hypothyroidism. Basal plasma T3 values ranged from 20 to 55 ng/100 ml with a mean of 36.2 vs 55–160 ng/100 ml with a mean of 107. Moreover, plasma T3 response to TRH, although present, was markedly lower than in the controls (20–90 ng/100 ml with a mean of 62 vs 100–175 ng/100 ml with amean of 127). Plasma TSH response to TRH appeared markedly delayed and prolonged (maximal rise at 60 min instead of at 20 min). Also of interest were the results obtained from studies of the corticotropic function. The maximal plasma ACTH values after insulin-induced hypoglycemia was 91 + 17.5 ...

Hypothalamic control of thyroid function in Amphibia

The regulation of thyroid activity in Amphibia is characterized by a wide range of variation in the dependence of the thyroid upon the pars distalis of the pituitary and in the dependence of the pars distalis upon the central nervous system. In Bufo bufo, thyroid activity is dependent upon TSH secretion from the pars distalis. Pars distalis thyrotropic activity is fully dependent upon contact with the hypothalamus. Hypothalamic influence includes a stimulatory part (TRH-secreting cells), situated in the hypothalamus at or behind the level of the optic chiasma, and an inhibitory part, originating above the level of the optic chiasma. The implications of this system are discussed. In most other Amphibia, thyroid activity—measured as iodine uptake—depends upon a functional pars distalis, but thyrotropic secretion shows a higher degree of autonomy, in that ectopic pars distalis grafts can maintain at least normal thyroid activity, and partial extirpation of the hypothalamus does not abolish thyrotropic activity. In some amphibian species a hypothalamic inhibitory influence upon thyroid activity is indicated. Triturus cristatus shows a further increase in autonomy, insofar as hypophysectomy does not result in immediate decrease in iodine uptake, as in other amphibian species. After some weeks, however, thyroid activity declines. The presence of hypothalamic inhibition in several amphibian species together with the fact that hypothalamic stimulation of thyrotropic function is necessary to complete amphibian metamorphosis, indicates that the basal pattern of thyroid regulation in Amphibia includes both inhibitory and stimulatory influences from the central nervous system.

Responses to thiourea and to surgical thyroidectomy by the autotransplanted pituitary gland in the red spotted newt

Two tests of thyrotropic function were conducted on autotransplanted pituitary glands in red spotted newts, Notophthalmus (Diemictylus, Triturus) viridescens viridescens, Rafinesque. In the first of these, the engrafted newts together with intact control animals were maintained in aqueous solutions of thiourea for 150 days. A marked goitrogenic response was seen in half the intact animals and in slightly more than a third of the animals with autotransplanted pituitary glands. In the second test, other newts with autotransplants and newts with intact pituitary glands were kept in thiourea and were also thyroidectomized surgically. Representative groups were killed at 15, 30 and 60 days after thyroidectomy. Thyroidectomy cells appeared in most of the intact and autotransplanted pituitary glands of newts killed at 30 and 60 days after thyroidectomy but not at 15 days. In similar tests mammalian glands have failed to support either goitrogenesis or the formation of thyroidectomy cells. It follows, then, that the transplanted pituitary gland of the newt is more active thyrotropically than those of the mammals thus far examined. Reasons for this difference are discussed.

Effect of chlorpromazine on thyroid function and thyrotropic function of the pituitary in rats with induced tumors

Effect of chlorpromazine on thyroid function and thyrotropic function of the pituitary in rats with induced tumors

Effect of transplanted tumors on the thyrotropic function of the pituitary

Effect of transplanted tumors on the thyrotropic function of the pituitary

Function and cytology of the normal and autotransplanted pars distalis of the hypophysis in the toad Bufo bufo (L)

The functional activity of the pars distalis following heterotopic and homoiotopic autotransplantation has been studied in adult toads of both sexes in the spring, about a month after breeding, and in the autumn on toads with mature gonads. Gonadotropic Function. In males, the homoiotopic grafting of the pars distalis maintained about normal spermatogenesis and interstitial cell activity, but ectopic transplants caused a strong reduction of interstitial cell activity, though spermatogenesis was only slightly reduced. In the spring experiment, there was no significant difference in the ovaries of the two graft-bearing groups, which were intermediate between the normal and the hypophysectomized controls. In autumn females, however, the ovaries of 5 of 8 toads with homoiotopic grafts atrophied, as in the hypophysectomized controls. The 3 remaining toads had ovaries of nearly normal size filled with mature eggs, but there were strong indications that in these 3 toads also the mature eggs that were present at the time of operation degenerated immediately after the operation, and was followed by a phase of extensive growth and maturation of small oocytes during the 2 months of the experiment. All females with ectopic grafts had atrophic ovaries at the end of the experiment. Adrenocorticotropic Function. This function was normal in the toads with homoiotopic grafts. No corticotropic function could be demonstrated in the ectopic grafts although the cytological study of males in the spring experiment showed that, in general, the adrenocortical cells in the toads bearing ectopic grafts appeared more active than those in the hypophysectomized controls. Thyrotropic Function. Thyroidal uptake of 131I in the autumn experiment was used to evaluate thyrotropic function. Uptake was normal in toads with homoiotopic grafts, but reduced in the toads with ectopic grafts. In the males with ectopic grafts, the 131I accumulation in the thyroids was not significantly higher than in the thyroids of the hypophysectomized controls. Fat Bodies. In the autumn experiment, feeding was insufficient to maintain body weight, and the fat bodies were greatly reduced in both normal controls and in the toads with homoiotopic grafts. Hypophysectomized controls, however, possessed large fat bodies despite an even greater loss of body weight. In the toads with ectopic grafts, net mobilization of fat from the fat bodies was intermediate between the normal and hypophysectomized controls. In the spring experiment, feeding was efficient. All groups increased in weight, and all showed fat deposition. Cytology of Pars Distalis. Four of the five tinctorial cell types, described for the pars distalis of Bufo bufo, were observed: carminophils, orangeophils, globular basophils, and violet cells. In most of the controls the carminophils and orangeophils were storing secretory granules; the globular basophils and the violet cells showed signs of secretory activity. All four cell types remained largely unchanged in the area of the homoiotopic grafts, bordering the median eminence and pars intermedia. In the rest of such grafts and in the heterotopic transplants cysts were formed, and degeneration and dedifferentiation of cells took place; carminophils and orangeophils had slightly degranulated, globular basophils had become strongly regressed in number and granulation, and violet cells had almost completely disappeared. Generally, there existed a close correlation between the state of the target organs and the morphological signs of secretory activity of the pars distalis cells. It is suggested that not only the globular basophils, but also the violet cells have a gonadotropic function, and are responsible for the development and maintenance of the interstitial Leydig cells in the testis.

NEUROENDOCRINOLOGY.

Regulation of Thyrotropic-Hormone SecretionInitially conceived of as a sluggishly reactive system concerned primarily with long-term metabolic adjustments, the pituitary-thyroid axis has been shown to be quickly responsive to changes in blood levels of thyroid hormone,126 , 127 to changes in the external environment126 and to acute disturbances in brain function such as hypothalamic stimulation.128 As with the other pituitary-target-gland systems, impressive evidence has been marshaled that indicates that the regulation of thyrotropic function is influenced both by a feedback system involving thyroid and pituitary glands and by neural influences. How these two systems of control are integrated has been the subject . . .

Azocarminophil cells of the toad adenohypophysis after mercaptoimidazol or radioiodothyroidectomy

Equivalence is shown between the azocarminophil cells of the adenohypophysis of the Bufo arenarum Hensel and similar cells described by other authors in different species of amphibians. The administration of methylmercaptoimidazol or I 131 produces characteristic changes in the azocarminophil cells. The existence of azocarminophil cells in the pituitary of Xenopus laevis is established. The thyrotropic function of azocarminophil cells is postulated.

The influence of hormones of the posterior hypophyseal lobe on the stimulated thyroid gland

When an excess of pituitrin P is given to male rats thyroid function is depressed although the hypophyseal thyrotropic hormone content remains normal. If 6-methylthiouracil and pituitrin P are given together the gland responds to the thiouracil in the normal way, although under these conditions there is no increase of hypophyseal thyrotropic function.

Neuroendocrine control of thyrotropin secretion in the rat.

The participation of 2 control mechanisms in the regulation of pituitary thyrotropic function by the hypothalamus was evaluated. Blood flow measurement by Sapirstein's Cardiac Output Distribution method in rats showed that extensive anterior hypothalamic lesions do not limit adenohypophysial blood flow and do not prevent the increase in thyroidal blood flow observed after goitrogen feeding, even when they block gland hypertrophy. Thus, the hypothalamic influence over pituitary thyrotropic function does not appear to be mediated through the control of pituitary blood flow. The participation of a neurohumor of hypothalamic origin was established in experiments in which the pituitary was separated from the hypothalamus without disrupting the vascular supply of either tissue. By joining in parabiotic union a rat whose anterior hypothalamus had been destroyed by electrocoagulation with a hypophysectomized partner, it was shown that the intact hypothalamus of the hypophysectomized partner, acting across the parabiotic union, could reverse the “goiter block” induced in the partner with the pituitary by the hypothalamic lesion. TSH did not cross the parabiotic union efficiently. The neurohumor stimulating TSH secretion across the union appeared to have a half-life in the circulation of the donor animal of the order of several hours, and exerted its effect across the union even in the presence of pituitary remnants in the donor.

Neurosecretion in birds

Morphologically the hypothalamic neurosecretory system of birds includes (1) two rather diffuse neurosecretory nuclei, the paraventricular nucleus and supraoptic nucleus which, according to the species concerned, consist of several more or less distinct divisions; (2) two hypothalamo-hypophysial neurosecretory tracts, the paraventriculo-hypophysial tract and the supraoptico-hypophysial tract, which are not separately identifiable in many species; (3) the neurosecretion-rich infundibular branches of the hypothalamo-hypophysial neurosecretory tract in the median eminece; and (4) the neurohypophysis and the neurosecretory fibers leading thereto. Specific functions cannot be assigned as yet to the individual neurosecretory nuclei or to their divisions. For the distal parts of the system, functions may be divided into those of the neurohypophysial and eminential components. The former is identified primarily with the regulation of water balance and apparently also with the ecbolic function in ovulation. The hormone involved is probably arginine vasotocin which is probably produced by hypothalamic neurosecretory cells and transported in association with the stainable neurosecretory material via the hypothalamo-hypophysial neurosecretory tract to the posterior lobe. Although oxytocin occurs in the posterior pituitary its function is unknown. The eminential component, whose radial neurosecretory fibers emanate from the eminential plexus and extend outwardly into juxtaposition with the primary capillaries of the hypophysial portal system, is primarily involved in control of the function of the adenohypophysis. This component is best known from the studies on species in which the gonadotropic function of the adenohypophysis is photoperiodically controlled. To us, the best hypothesis of the general functional mechanism of the eminential component is that the “releasing factor” or “releasing factors” are formed in hypothalamic neurosecretory cells where they become associated with neurosecretory material, which is usually stainable with aldehyde-fuchsin or chromalum hematoxylin, and which passes via neurosecretory fibers into the radial fibers of the zona externa of the median eminence. It seems evident that the control of the adenohypophysis is exerted primarily through the transfer of such “releasing factors” from these fibers into the primary capillaries of the portal system. It is possible that this transfer involves a functional relationship between the neurosecretory fibers and fibers from the nonneurosecretory tubero-hypophysial tract. The very fragmentary data available suggest that the gonadotropic function of the adenohypophysis is almost completely dependent on such “releasing factors” although the gland does have basic adrenocorticotropic and thyrotropic functions that are independent of the median eminence. However, higher levels of thyrotropic and adrenocorticotropic activity by the adenohypophysis apparently require the appropriate “releasing factors”.

The hypophysis of Xenopus laevis Daudin larvae after removal of the anterior hypothalamus

The region of the brain anterior to the tectum opticum, including the nucleus magnocellularis praeopticus , and other possible sites of anterior hypothalamic centers, has been removed from larvae of Xenopus laevis , the hypophysis being left intact. The larvae, the rate of development of which was somewhat delayed, have been reared for variable periods of time. In the absence of the hypothalamic neurosecretory nuclei the pituitary neural lobe underwent a complete regression and was therefore wholly lacking. In the pituitary distal lobe both acidophilic and thyrotropic cells appeared to be cytologically well-differentiated. After thiouracil administration a clear-cut goitrogenic response was shown by the thyrotropic cells; some acidophilic cells (presumably somatotropic ones) showed normal features, while abnormally large acidophilic granules occurred in certain other specifically located ones (presumably ACTH-secreting cells), indicating some possible cell disturbances. The possibility that the thyrotropic function of the pituitary is, at least in part, independent of the hypothalamus seems further supported by the results obtained in the present experiments. The lack of the neural lobe was accompanied by hypertrophy of the intermediate lobe. Hyperactivity was indicated by the hypertrophy and marked pyroninophilia of both the cytoplasm and nucleoli of its cells. In correlation with this, a higher pigmentation than normal was shown by the operated larvae, in which tightly packed and diffusely pigmented melanophores were seen to occur. The present findings are compared with other available data, and their significance is briefly discussed.

Hypothalamic influences on heterotropic pituitary in the rat.

Anterior pituitaries from neonate rats grew well in the eyes of hypophysectomized recipients and supported a considerable degree of thyroid function as judged by a number of tests. Anterior hypothalamic lesions in the ‘thyrotropin area’ had no effect upon the growth or function of these grafts. The results are discussed with respect to the neurohumoral theory of hypothalamic control over pituitary thyrotropic function.

The Importance of the Stalk Connexion for the Power of the Anterior Pituitary of the Rat to React Structurally upon Ceasing Thyroid Function.

Summary.Complete section of the pituitary stalk in the rat prevents hypertrophy and vacuolization from arising in the basophil cells of the anterior hypophyseal lobe after thyroidectomy. If the pars tuberalis connexion is left intact, however, these cell‐changes do not fail to appear. When the posterior and middle lobes have been extirpated, typical cell‐changes arise in the anterior lobe after thyroidectomy.The changes in the basophil cell‐picture are interpreted as a morphological sign of an increased thyrotropic function. Therefore, the thyrotropic function of the anterior pituitary lobe is regarded as highly dependent on the stalk connexion with the hypothalamus. The system composed of the hypothalamus, stalk and anterior lobe reacts to thyroid insufficiency independently of the intermediate and posterior lobes and the nerve fibres running through them. The view that the thyrotropic function of the anterior lobe is essentially controlled without the assistance of the stalk seems to be untenable.

THE EFFECT OF REFEEDING AND OF THE ADMINISTRATION OF A PITUITARY EXTRACT ON THE OVARIES OF UNDERNOURISHED GUINEA PIGS1

IN A PREVIOUS PUBLICATION (1) it was shown that undernutrition of the guineapig resulted in marked structural changes in the thyroid, characterized by atrophy and flattening of the acinar epithelium and retention of colloid suggesting a resting, inactivegland. Refeeding resulted in a rapid gain in body weight and return of thyroid structure to normal. The thyroid of the undernourished animals was markedly sensitive to stimulation by the thyrotropic principle of the anterior hypophsis. Evidence was presented which indicated that the structural changes observed in the thyroid of the undernourished animalswere due to impairment of the thyrotropic function of the anterior pituitary. The changes occurring in the ovaries of these animals are described in the present communication. For this study mature, female guinea pigs, weighing approximately 300 gm., were selected. Details of the care and feeding of these animals have been described (1). Animals eating a full diet were killed while gaining weight, to serve ...

Initiation and early development of thyrotropic function in the incubating chick

Initiation and early development of thyrotropic function in the incubating chick

THE REGULATION OF THYROTROPIC FUNCTION BY THYROXIN AFTER PITUITARY STALK SECTION

THIS PAPER reports part of a series of experiments designed to clarify the mechanisms regulating the secretion of thyrotropin. More specifically, it seeks to J L answer the question as to whether fluctuations in an animal's thyroxin level affect the secretion of thyrotropin by direct humoral access or through the mediation of the hypothalamo-hypophyseal system. When considering the regulation of thyrotropic function, at least three possible mechanisms must be taken into account. These possibilities are: (a) nervous influences through the cervical sympathetics; (b) impulses passing through the hypothalamo' hypophyseal stalk and (c)direct humoral influences. Evidence has previously been presented indicating that cervical sympathectomy can slightly and temporarily decrease thyrotropic function, although the sympathetics are not necessary for continued normal thyroid function (1). Subsequently the r6le of the hypothalamo-hypophyseal pathways was studied in reference to the regulation of thyrotropic function. ...