Supraoptico-hypophyseal Tract Research Articles

Pituitary Macroadenoma: A Case of Balanced Deficiencies

Abstract Introduction: Diabetes insipidus (DI) rarely occurs in pituitary tumors although some patients may develop DI following pituitary tumor resection. However DI is known to occur in patients with tumors metastatic to the pituitary or in infiltrative disorders of the pituitary gland. We are reporting a patient with a 2 cm pituitary macroadenoma whose DI was unmasked by glucocorticoid therapy. Case Presentation: A 61-year-old male with a history of non-functioning pituitary macroadenoma, incidentally discovered on imaging in 2015 and stable at 1.6cm for 4 years, was referred to endocrinology for interval enlargement of his macroadenoma. He had presented to primary care due to new headache during extreme physical exertion, but otherwise denied any symptoms such as vision loss, fatigue, decreased libido, weight loss, or urinary frequency. Repeat MRI indicated growth to 2.1cm in the suprasellar component, no cavernous sinus involvement, and abutting the optic chiasm. Laboratory results revealed new onset central hypothyroidism (FT4 0.21 ng/dL (ref 0.78-2.19) with triiodothyronine 68 ng/dL (ref 80-200) and TSH 1.61 mIU/L (ref 0.47-4.68), central hypogonadism (Testosterone Free 1.3 pg/mL (ref 6.6-18.1)) and concern for adrenal insufficiency with a cortisol of 4.4 mcg/dL. He was empirically started on hydrocortisone replacement until an ACTH stimulation test could be completed, and after 3 days instructed to begin low dose levothyroxine replacement. At close followup, patient revealed that he developed new hourly nocturia causing significant distress. An overnight water deprivation test yielded a serum sodium 152 mmol/L with a urine osmolality 191 mOsm/kg, both rapidly improving with intravenous desmopressin. Copeptin was 4.6 pmol/L. Discussion Diabetes insipidus occurring in pituitary tumors including macroadenomas is extremely rare. Secretion of AVP occurs in the hypothalamic osmoreceptors, supraoptic or paraventricular nuclei, and the superior portion of the supraopticohypophyseal tract. AVP deficiency is most commonly due to damage to these areas either through neurosurgery or trauma, and more rarely tumors or infiltrative disease. However, glucocorticoid and thyroid replacement each may precipitate the development of diabetes insipidus. Well described in literature, glucocorticoid deficiency and hypothyroidism each independently impairs free water excretion. Low cortisol stimulates release of antidiuretic hormone, but this secretion is then inhibited by exogenous steroid replacement. Cortisol interferes with AVP signaling through unclear mechanisms either at the V2 receptor or post-receptor level, decreasing translocation of type 2 aquaporins and therefore reducing free water reabsorption. It is important to recognize that CDI can be unmasked after glucocorticoid or thyroid hormone replacement.

VASOPRESSIN IN INTENSIVE CARE UNIT

Vasopressin increases the serum level of IGF, binding protein-1 (IGFBP-1) in humans through V2A receptor (1), a fact related with the adequate interpretation of the high IGF binding protein-1 (IGFBP-1) level, as predictor marker of gravity in critically ill patients in intensive care units (ICU). Both vasopressin and IGFBP-1 are good prognostic markers for survival in highly stressful conditions such as the acute myocardial infarction (2,3). Arginin Vasopressin (AVP) is the first peptide hormone synthesized (4), and for a longtime has been used only for its antidiuretic properties, maximally amplified by biochemists in its analogues deamino-D-arginin vasopressin (DDAVP) (5). However AVP is not the single antidiuretic peptide hormone. Its phylogenetic ancestor arginine vasotocin (AVT) is the main antidiuretic hormone of all vertebrates, excepting mammals, and its relative oxytocin – also shows antidiuretic activities (revealed by water intoxication in pregnant women, excessively infused with oxytocin). By reverse, in the disease with vasopressin deficiency central diabetes insipidus, although the levels of serum vasopressin are low, there is an increased antidiuretic activity of the cerebrospinal fluid in adult patients (6). There are some difficulties in identifying nonapeptides and their origins (7), but there are data about sources of antidiuretic hormone, outside the wellknown hypothalamic nuclei, for example, in pancreas (8), in the adrenal gland, in human pineal fetal cells (9), in pineal gland of rats with hereditary central diabetes insipidus (10). A network of vasopressinergic fibers is spread within the brain, independent of supraoptico-hypophyseal tract. The relation of vasopressin with melatonin (11), was proved, as well as the relation with the brain visual evoked potentials (12). Three types of receptors produce vasopressin effects: V1A, in smooth muscles vessels and brain, V1B in pituitary and brain structures and V2 in kidney. The V2 receptors mediates the antidiuretic effect, i.e. activates the free water transport in Editorial

Changes of Serum ADH Level during Matoidectomy under General Anesthesia

Background: Markedly reduced urine have been commonly observed during mastoidectomy under general anesthesia. The aim of study was to evaluate the surgery-related mechanism of reduced urine during mastoidectomy. Methods: 11 patients undergoing mastoidectomy were studied. Blood samples were drawn from CVP line inserted through right internal jugular vein just before drilling (Pre-D); at 15 min after drilling (D-15); at the time closest to the inner ear (CHP-1); at 15 min (CHP-2) and 30 min (CHP-3) after CHP-1 and just before emergence (End). MAP, HR, temperature, CVP, and urine output (UO) were recorded at each period. 0.9% normal saline with room temperature was used to irrigate surgical field. Serum ADH, and the osmolalities (serum and urine) were measured. In 6 patients, serum TSH and FSH were measured, simultaneously. Results: There were no significant hemodynamic changes during procedure. UO was decreased in 50% during and after the drilling. No differences showed in UO between before and after the drilling of CHP. Plasma ADH level after the CHP was increased 2-3 fold than before. Serum osmolality was unchanged throughout the periods, while the urine osmolality was significantly increased after the period of CHP. FSH was not changed during the periods and TSH was decreased slightly than in Pre-D. Conclusions: Ｔhe reduced urine output during mastoidectomy may be influenced by the drilling-related vibration, which may affect the supraoptico-hypophyseal tract, resulting in ADH release. The irrigated isotonic saline with higher osmolality (308 mOsm/) than plasma osmolality may partly contributed to the increased ADH.

Triphasic AVP Secretion in Encephalopathy.

A patient with encephalopathy developed triphasic changes in the clinical course, starting with diabetes insipidus (DI), then the syndrome of inappropriate ADH secretion (SIADH), and followed by the final phase of DI. The clinical course of encephalopathy was very rapid. The patient lost consciousness completely within only one day after the onset. During the early phase, he lapsed into a condition of "brain death". We could not identify the etiology of the encephalopathy. The triphasic change referred to above is similar to previous reports of cats model after stereotactic destruction of the supraopticohypophyseal tract. We speculate that our case may have been associated with neurohypophyseal dysfunction caused by supraopticohypophyseal tract damage.

Diabetes insipidus with spontaneous remission

Pathogenesis of idiopathic diabetes insipidus is unknown and the clinical course of the disease is permanent. However, we observed one patient who was diagnosed of idiopathic diabetes insipidus spontaneously reverted after approximately 13 months. The cause and pathogenesis of the disease were not evident. However, some reversible abnormalities should have been encountered in the hypothalamic-neurohypophyseal system. It is suggested that some unknown reversible impairments of the supraopticohypophyseal tract can cause diabetes insipidus. This case represents a well-documented description of idiopathic diabetes insipidus with spontaneous remission.

Factors controlling adrenal weight and corticosterone secretion in male rats as revealed by median eminence lesions and pharmacological alteration of prolactin secretion

To determine whether or not prolactin, as well as ACTH, was involved in the control of adrenal weight and steroid release, lesions in the median eminence which had previoulsy resulted in impaired steroid release and atrophy of the adrenal were placed in animals in which the plasma prolactin was allowed to rise as a result of the lesions or prevented from rising by the administration of the dopamine agonist, CB-154. As previously reported, as the severity of diabetes insipidus (DI) increased as a result of interruption of the supraoptico-hypophyseal tract, adrenal weight declined reaching a nadir at water intakes of approximately 100–150 ml/day. This was followed by a reversal of this trend and an increase in adrenal weight as water intakes increased further. These effects were not modified by CB-154 which was effective to lower the elevated prolactin levels in the animals. In general, adrenal weight correlated with levels of plasma corticosterone and progesterone. The ability of the animals to undergo compensatory adrenal hypertrophy was also impaired by median eminence lesions in the presence or absence of CB-154. Exceptional animals were encountered in which adrenal weight was high and yet plasma corticosterone was low. Treatment of hypophysectomized animals with long-acting ACTH plus maintenance doses of triiodothyronine prevented the adrenal atrophy characteristic of the hypophysectomized animal, thus confirming that ACTH is the most important hormone in the control of adrenal weight. Some role for prolactin is suggested by the fact that elevation of prolactin via the drinking of sulpiride, a dopamine receptor blocker, was associated with a relatively small elevation of adrenal weight and plasma corticosterone. In the animals with lesions, blockade of adrenal function was always found in animals with complete lesions of the median eminence and was usually found if the lesion destroyed the anterior median eminence and extended caudally to the separation of the pituitary stalk. Lesions of the paraventricular nucleus did not block adrenal function, presumably because sufficient CRF neurons were located outside this structure to maintain adrenal function and/or because of the maintenance of considerable vasopressin secretion. Defective adrenal function was usually associated with DI indicative of interruption of the supraoptico-hypophyseal tract and deficient vasopressin secretion; however, several animals were found which had relatively high degrees of DI and yet adrenal function was relatively normal suggesting that CRF is more important than vasopressin in the control of ACTH secretion. Since some animals had relatively normal adrenal function and weight in the presence of severe damage to the median eminence it is possible that other pituitary factors, the release of which would be increased by such lesions, such as α-MSH, may play a role in maintenance of adrenal weight. The possible participation of neural factors also cannot be ruled out.

Morphological changes of rat neurosecretory neurones after stereotacix injection of kainic acid into the supraoptic nucleus or the supraoptico-hypophyseal tract

Kainic acid is a structural analogue of glutamic acid possessing neurotoxic property. In the present study, performed on rats, morphological changes of neurosecretory neurones after stereotaxic injection of kainic acid into the left supraoptic nucleus or into the left supraoptico-hypophyseal tract were investigated. It is shown that administration of kainic acid in a dose that leads to destruction of hippocampal pyramidal cells has no effects on supraoptic perikarya but does destroy neurosecretory axons. These results contradict the observations of many authors who reported that local injection of kainic acid into the brain causes degeneration of perikarya but leaves axons of passage unaffected.

Neurohemal contact in the internal zone of the rabbit median eminence

The concept of neurosecretion as the mechanism by which neural control of adenohypophyseal function is accomplished was based on the observation that long capillary loops penetrate deeply into the supraopticohypophyseal tract as it passes through the median eminence internal zone. However, neural contact upon these capillary loops has not been demonstrated in the mammalian median eminence. The present transmission electron microscopic investigation of the rabbit median eminence demonstrates neurohemal contact in the median eminence internal zone. Axons containing small lucent vesicles 53.3 +/- 3.28 nm in diameter (mean +/- SEM) or small lucent and large granular vesicles with a mean diameter of 122.4 (+/- 3.28 nm) in their terminals make neurohemal contact with capillary loops in the internal zone and form a cuff about them. These terminals resemble terminals found in the external zone. Intravenous injection of the false neurotransmitter 5-hydroxydopamine (5-OH-DA) renders small lucent vesicles granular in both the external and internal zone. The effect of 5-OH-DA injection is abolished by concurrent reserpine administration. Whereas large granular vesicles in many terminals become lucent after reserpine administration, in others they remained electron dense. Viewed in the light of previous studies our findings suggest that the internal plexus arises from the external plexus and invaginates the neuropil carrying connective tissue and parvicellular axon terminals of aminergic and peptidergic systems from the external zone into the internal zone, that some elements making neurohemal contact with long capillary loops are terminals of the noradrenergic reticular infundibular tract arising outside the hypothalamus in the brainstem, and that long capillary loops form a system of repeating microvascular modules which markedly increase the surface available for neurohemal contact.

Immunoreactive dynorphin and α-neo-endorphin in rat hypothalamo-neurohypophyseal system

Concentrations of dynorphin and alpha-neo-endorphin were measured in rat supraoptic and paraventricular nuclei, median eminence and posterior pituitary. Paraventricular lesions did not alter the level of either peptide in the median eminence or posterior pituitary. Knife cuts in the lateral retrochiasmatic area that severed the supraoptico-hypophyseal tract reduced dynorphin and alpha-neo-endorphin levels by 64-80% in the posterior pituitary and by somewhat less in the median eminence. Knife cuts in the vicinity of the supraoptic nucleus that did not interrupt the supraoptico-hypophyseal tract did not affect peptide concentrations in the posterior pituitary. Our data suggest that dynorphin and alpha-neo-endorphin in the posterior pituitary are in processes of supraoptic nucleus neurons. These neurons also project to the median eminence which may receive fibers from other dynorphin and alpha-neo-endorphin containing cells too.

On Hypothalamic Control of Ovulation in the Turkey

Small bilateral lesions of the ventromedial preoptic hypothalamus consistently blocked ovulation. Lesions that completely cut the supraoptico-hypophyseal tract or that were placed throughout the tuberal hypothalamus and median eminence had no effect on ovulation. Lesions placed in the posterodorsal, medial, and ventral parts of the infundibular nuclear complex and in the medial and posteria divisions of the median eminence resulted in slight to moderate atresia of rapidly growing follicles within 38 to 40 hr after surgery.

Hypothalamic neurons secreting vasopressin and neurophysin

Vasopressin is synthesized in the magnocellular system of the hypothalamus in clusters of cells which form the supraoptic nucleus and the paraventricular nucleus. The hormone is synthesized and packaged in neurosecretory granules with an intragpanular protein, neurophysin. The demonstration of axon flow of neurosecretory granules from the perikarya in the hypothalamus to the posterior lobe of the pituitary and subsequent release into the blood has been an important historical chapter in our understanding of neurosecretion. Isolation of neurophysins from several species and development of antisera to these peptides as well as antibodies to vasopressin have provided new tools to re-examine this system. In several species, the data indicate a specific neurophysin for vasopressin and a different neurophysin for oxytocin. It is now well established that neurophysins are secreted with hormones and this has provided a cogent argument that exocytosis is a major form of neurosecretion of vasopressin. Assay of neurophysin in plasma can be used to study vasopressin release. Immunohistochemical studies using antibodies to vasopressin and neurophysin demonstrated that the magnocellular system is more diffusely distributed throughout the hypothalamus than was previously appreciated. In addition, vasopressin and neurophysin are formed in both the supraoptic and paraventricular neurons and there are three pathways of secretion. The major pathway is the supraoptico-hypophyseal tract to the posterior lobe. The second pathway is to the external zone of the median eminence for secretion into the hypophyseal portal blood. The third pathway is to the third ventricle for secretion into cerebral spinal fluid. Vasopressin in the external zone is greatly increased by the absence of adrenal cortical steroids which suggests that vasopressin may play a role in the hypothalamic anterior pituitary adrenal axis. The cerebral spinal fluid pathway may be important in man if vasopressin is found to have the memory consolidating effects which have been investigated in other animals.

Identification and terminal distribution of the tubero-hypophyseal monoamine fibre systems in the rat by means of stereotaxic and microspectrofluorimetric techniques

Summary The monoamine-containing fibres to the median eminence and the neurointermediate lobe have been studied by fluorescence microscopy in combination with microknife lesions. The origin and the course of the fibres were evaluated on the basis of monoamine accumulation proximal to the lesion and monoamine disappearance distal to the lesion. The nature of the monoamines stored in the various fibre systems was characterized with microspectrofluorimetry. Five groups of monoamine-containing axons were seen to enter the median eminence: (a) A large group of dopamine axons which originated in cells of the arcuate nuclei and the ventral parts of the anterior periventricular nuclei; they entered the fibre layer of the median eminence close to the infundibular recess. (b) A large group of noradrenaline axons which originated in areas outside the mediobasal hypothalamus; they entered the anterior median eminence from the lateral side, close to the brain surface, and intermingled with the arcuato-hypophyseal dopamine fibres in the internal layer and the deeper part of the external layer of the median eminence. (c) Two minor groups of catecholamine axons: one reached the median eminence from the anterior side, with an antero-posterior direction, probably mingled with the axons of the supraoptico-hypophyseal tract; the other ran into the arcuate nucleus with a dorso-ventral course along and close to the third ventricle; the fibres could not be traced further. (d) A small group of scattered axons containing an unidentified fluorigenic substance which differed microspectrofluorimetrically from the catecholamines and 5-hydroxytryptamine. Judging from the disappearance of monoamines distal to the lesion and from the chemical and microspectrofluorimetric analyses of the catecholamines in the median eminence and the neuro-intermediate lobe, the following conclusions concerning the terminal ramifications of the catecholamine fibre systems could be drawn: The arcuato-hypophyseal dopamine neurones give rise to one part of the terminals in the zona externa of the median eminence and to most, possibly all, terminals in the zona interna. The tubero-hypophyseal noradrenaline fibres also have their terminals in the zona externa, and they contribute to the catecholamine innervation of the neuro-intermediate lobe. Many studies on the functional role of aminergic mechanisms in the hypothalamic regulation of the pituitary functions have focussed on the presence of dopamine in the median eminence. The present investigation has demonstrated two prominent neurone systems in the hypothalamo-pituitary complex: one containing dopamine, the other containing noradrenaline. Moreover, the results suggest the involvement of a third neurone system, probably containing an indole derivative.

Neurosecretory material in the supraoptico-hypophyseal tract of the bat throughout the hibernating and summer periods.

AbstractNeurosecretory material in the supraoptico‐hypophyseal tract of 151 hibernating and summer bats (Myotis lucifugus lucifugus) was studied in chromealum‐hematoxylin‐phloxine‐stained serial sagittal sections. Seasonal variations of neurosecretory content throughout the hibernating period (mid‐September through mid‐May) and “active” summer period (June to mid‐September) were observed and the staining density of the neurosecretory material in the supraoptic nucleus, infundibular stem and pars nervosa was “quantitated” visually. Cell counts and measurements also were made to determine if cell number and size changes accompanied seasonal changes in neurosecretory content.A significantly greater staining density of neurosecretory material in the supraoptico‐hypophyseal tract of the hibernating bats, than in the “active” animals was observed. These differences were always greater in the infundibular stem than in the supraoptic nucleus and pars nervosa. Although there was no correlation between seasonal activity and the total number of neurosecretory cells in each brain, there was always a smaller number of dark‐staining cells in the “active” bats than in those that were hibernating. Nucleocytoplasmic ratios of hibernating bats were below those of the active animals. These resulted from smaller nuclear and larger cytoplasmic sizes during hibernation than in the summer. Nucleolar sizes, however, were slightly greater in the hibernating bats than in the active animals. The significance of these results in terms of seasonal activity is discussed.

Gonadotropic activity of neonatal pituitary glands implanted in the rat brain.

Pituitary glands of neonatal rats were implanted by stereotaxic methods in various hypothalamic areas of the brains of adult, hypophysectomized male rats. Of 58 implantations, 44 viable grafts composed of pars distalis, intermedia, and epithelioid-like nervosa were found 3 months later. In none of the graft-bearing animals was there any evidence of thyrotropic or corticotropic activity as judged by thyroid or adrenal weight, I131 uptake, or plasma free corticosteroids. In 18 graft-bearing animals, testicular weights ranged from 831 to 2,118 mg, compared to mean testis weight of 165 mg for hypophysectomized, nonimplanted animals. Histological sections of testes from these graft-bearing animals revealed active spermatogenesis. In each implanted animal with testicular maintenance, the pituitary graft was situated in the floor of the hypothalamus, encroaching upon or interrupting fibers of the supraopticohypophyseal tract. Adenohypophyseal cells which appeared to be nearest or more intimately related to these fibers were large (12–20µ), vacuolated, and contained abundant fuchsinophilic granules typical of castration cells. Other chromophil types were not present. In all nonfunctional grafts (situated in preoptic area, septum, anterior hypothalamus, and mammillary region) adenohypophyseal cells were uniformly small and chromophobic.

Diabetes Insipidus Following Section of Hypophyseal Stalk

THOUGH considerable progress in the understanding of the anatomv, physiology, and pathology of dial~etes insipidus has been made, there still remain aspects of this process that are in a state of controversy or are unknown. The significance of Cajal's 39 observation in 1894 of a nerve tract joining the hypothalamus with the hypophysis, was originally not fully appreciated, for in the early part of the ~Oth century diabetes insipidus was thought to be the result of deficiency of secretion from the posterior lobe of the pituitary body. Camus and Roussy 4 showed that this condition could occur following damage to the hypothalamus alone. The appreciation of the importance of the fiber tract joining the posterior lobe of the pituitary body to the hypothalamus by Pines 37 and Greving, 15 gave further impetus to the idea that these structures functioned as a unit rather than separately. Using the Horsley-Clarke ~a stereotaxic instrument, Fisher et al. ~3 found that when hypothalamic lesions in cats interrupted the supraopticohypophyseal tract bilaterally, the daily volume of urine was greatly increased. I t was also observed that administration of posterior pituitary extract decreased the polyuria. Microscopic examination of the hypothalamus in the animals showing polyuria revealed that both supraopticohypophyseal tracts had been sectioned. The marked loss of supraopticohypophyseal fibers was associated with loss of nerve cells in the supraoptic nuclei. The essential features observed in cats were also found by Magoun et al. 29 to apply to monkeys, with the additional observation that section of the infundibulum resulted in a mild to moderate polyuria, whereas section of the median eminence resulted in severe polyuria. Using a method of remote stimulation, HarrislT,,S furthered the concept of functional unity of the hypothalamohypophyseal system. When the tip of an electrode was in contact with the hypothalamic portion of the supraopticohypophyseal tract, median eminence or infundibulum, stimulation caused inhibition of water diuresis which varied from 15 minutes to several hours, depending upon the strength of the stimulus. This inhibition of water diuresis was the result of release of the antidiuretic hormone. Although PoppV s had suggested that the hypothalamus was a secretory center, it remained for Scharrer and Gaupp 45 to show evidence of neurosecretion in man. Investigations of Hild and Zetler 21,22 and others 34,46 suggested that the antidiuretic hormone is produced by cells of the hypothalamus and then transported down the hypophyseal stalk to be stored in the posterior lobe of the pituitary gland. Although general acceptance of an interrelated hypothalamohypophyseal system has been largely achieved, some disagreement has persisted as to the relationship of section of the pituitary stalk to diabetes insipidus. Paulesco, ~ in 1908, mentioned briefly the results of section of the pituitary stalk in 6 dogs with survival periods ranging from 1 to 24 days, but made no mention of water balance other than to comment on the lack of glycosuria in 1 dog. In their experiments on hypophysectomy, Crowe et al. 6,7 included 5 dogs in which division of the pituitary stalk was done. No mention was made of diabetes insipidus. In later studies on dogs, Cushing and Goetsch 8

Long-term effects of diencephalic lesions on the ovary of the hen.

Small lesions produced electrolytically in the median diencephalon of actively ovulating hens caused most of them to cease ovulation regardless of the site of lesions. The duration of the nonovulating period thus induced, however, tended to vary with position of the lesions. When in the preoptic hypothalamus, supraoptico-hypophyseal tract, or dorsocaudal thalamus, the mean periods of interruption were about twice that found when lesions were in the central diencephalon. Considerable variability was encountered, however. A possible explanation is offered for the differing rates of functional recovery which occur following the placement of lesions.

CHANGES IN SALT AND WATER DISTRIBUTION, BLOOD PRESSURE, AND ADRENAL ACTIVITY FOLLOWING NEUROHYPOPHYSEAL DENERVATION IN THE RAT

Diabetes insipidus was induced by stereotaxic placement of a small lesion in the supraopticohypophyseal tract at the median eminence of the hypothalamus. The presence of diabetes insipidus was indicated by a polyuric response to an imposed salt load which, even with rigid selection criteria, occurred in a high percentage of lesion-bearing animals. In some animals the polyuric response was observed as early as the second postoperative day. No sign of remission was observed within the 4 week period of observation. Extracellular fluid volume and calculated extracellular sodium were increased in the diabetic rats. Basal blood pressure was reduced while sensitivity to norepinephrine and to pitressin was enhanced. The lesion was followed also by a reduction in gonadotrophic activity as indicated by a marked reduction in testis size.

Extrarenal factors in diabetes insipidus in the rat.

Using inulin as indicator of the extracellular volume, the distribution of sodium, potassium and water was studied in rats with diabetes insipidus produced by interrruption of the supraoptico-hypophyseal tract. A well defined increase in the extracellular fluid volume associated with normal plasma sodium and reduced plasma potassium concentration was uniformly present in the rats with diabetes insipidus. These changes occurred in nephrectomized animals and were thus independent of renal function, but were in some degree referable to an increase in adrenal function since they could be partially reversed by adrenal ablation.

CHANGES IN SALT AND WATER DISTRIBUTION, BLOOD PRESSURE, AND ADRENAL ACTIVITY FOLLOWING NEUROHYPOPHYSEAL DENERVATION IN THE RAT

Diabetes insipidus was induced by stereotaxic placement of a small lesion in the supraopticohypophyseal tract at the median eminence of the hypothalamus. The presence of diabetes insipidus was indicated by a polyuric response to an imposed salt load which, even with rigid selection criteria, occurred in a high percentage of lesion-bearing animals. In some animals the polyuric response was observed as early as the second postoperative day. No sign of remission was observed within the 4 week period of observation. Extracellular fluid volume and calculated extracellular sodium were increased in the diabetic rats. Basal blood pressure was reduced while sensitivity to norepinephrine and to pitressin was enhanced. The lesion was followed also by a reduction in gonadotrophic activity as indicated by a marked reduction in testis size.

Evidence for a role of the supraopticohypophyseal system in regulation of adrenocorticotrophin secretion.

Conclusions1. Hypothalamic lesions which block ACTH secretion, as judged by adrenal ascorbic acid depletion, adrenal weight, or blood ACTH concentration, uniformly destroy a significant fraction of the supraopticohypophyseal tract as evidenced by their location and the presence of diabetes insipidus. 2. ACTH secretion appears to be produced in these rats by large doses of pitressin. 3. Control of diabetes insipidus by small doses of pitressin, or the injection of epinephrine, histamine or pitocin does not produce significant ACTH secretion in such rats. 4. The results indicate that the supraopticohypophyseal tract may play a role in the regulation of ACTH secretion by release of antidiuretic hormone into the hypophyseal portal vessels.