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Longitudinal imaging reveals pituitary enlargement preceding hypoplasia in two brothers with combined pituitary hormone deficiency attributable to PROP1 mutation.

Mutations of the PROP-1 gene cause combined pituitary hormone deficiency. Progressive ACTH/cortisol insufficiency is found in a few patients. Congenital hypoplasia of the anterior pituitary gland is the most common magnetic resonance imaging finding in patients with PROP-1 mutations. We present two brothers with compound heterozygosity for the two mutations 150delA and 301-302delAG of the PROP-1 gene. Both showed combined pituitary hormone deficiency of GH, TSH, PRL, and gonadotropins, as is typical for PROP-1 deficiency. We observed a developing insufficiency of ACTH and cortisol secretory capacity in both patients. Computed tomography revealed an enlarged pituitary in the older brother at 3.5 yr of age. Repeated magnetic resonance imaging after 12 yr showed a constant hypoplasia of the anterior pituitary lobe. Similarly, magnetic resonance imaging of the younger brother showed a constant enlargement of the anterior pituitary gland until 10 yr. At the age of 11 yr, the anterior pituitary was hypoplastic. The reason for pituitary enlargement in early childhood with subsequent decrease in pituitary size is not known. We speculate that altered expression of early transcription factors could be involved. Because both patients have the same PROP-1 mutations and an identical pattern of combined pituitary hormone deficiency, we suggest that early pituitary enlargement may be the typical course in such patients in whom pituitary surgery is not indicated.

Child↗

Bacteremia-induced changes in pituitary hormone release and effect of naloxone.

Acute bacteremia in sheep caused a surge of plasma beta-endorphin/beta-lipotropin (beta-EP/beta-LPH) associated with shivering behavior, tachycardia, hyperthermia, hemoconcentration, and decreased respiration rate. The surge of plasma beta-EP/beta-LPH was immediately followed by increases (P less than 0.05) in plasma prolactin and growth hormone (GH) concentrations and a depression (P less than 0.05) of plasma luteinizing hormone. These changes in pituitary hormone release were consistent with opioid-induced changes described in the literature. To examine possible opioid mediation, naloxone (2.5 mg X kg-1 X h-1) was continuously infused intravenously from 3 h before to 3 h after induction of an E. coli bacteremia. With the exception of plasma GH, naloxone failed to alter any of the hormonal or clinical parameters associated with bacteremia. For plasma GH, naloxone delayed (P less than 0.01) the increase but did not attenuate its magnitude, suggesting that an opioid mechanism may influence the timing of the pituitary GH release resulting from bacteremia. In general, opioid mechanisms sensitive to the present dosage of naloxone do not appear to mediate bacteremia-induced changes in hormonal or clinical parameters.

Animals↗

Evolving pituitary hormone deficiency is associated with pituitary vasculopathy: dynamic MR study in children with hypopituitarism, diabetes insipidus, and Langerhans cell histiocytosis.

PURPOSE: To assess pituitary vascularization in children with hypopituitarism, central diabetes insipidus (DI), or Langerhans cell histiocytosis. MATERIALS AND METHODS: Dynamic MR images were obtained through the pituitary stalk after injection of gadopentetate dimeglumine in 21 patients (11 boys and 10 girls, aged 4-17 years) and 10 age-matched control subjects. RESULTS: Initial enhancement of the posterior pituitary lobe occurred simultaneously with that of the straight sinus in all subjects except four patients with central DI and a thick stalk. Enhancement of the entire anterior pituitary lobe was statistically significantly prolonged (P < .005) in the four patients with delayed initial posterior pituitary lobe enhancement. CONCLUSION: Fast-framing dynamic MR imaging provides new information on the blood supply of the hypothalamic pituitary area in normal and abnormal pituitary glands. Enhancement times exceeding 20 seconds for the posterior pituitary lobe and 30 seconds for the anterior pituitary lobe may suggest abnormal vascularization in the hypophyseal arteries and portal system.

Adolescent↗

Combined pituitary hormone deficiency due to the F135C human Pit-1 (pituitary-specific factor 1) gene mutation: functional and structural correlates.

The pituitary-specific transcription factor Pit-1 (pituitary-specific factor 1) is known to play a key role in the differentiation of PRL-, GH-, and TSH-secreting cells, and in the regulation of expression of the corresponding genes. In recent years, 12 distinct mutations of the Pit-1 gene have been shown to be responsible for a phenotype of multiple congenital pituitary hormone deficiency involving PRL, GH, and TSH. We had previously identified, in four siblings with GH, PRL, and TSH deficiencies, a mutation (F135C) resulting in a single amino acid change within the POU-specific binding domain of the Pit-1 molecule. In the present report, we have explored the functional effect of the F135C mutation. In vitro activity tests performed by transfection in human HeLa cells showed decreased transactivation capacity on the PRL, GH, and Pit-1 genes. The DNA binding experiments performed by gel shift showed that the F135C mutation generated a protein capable of binding to DNA response elements. To analyze how the F135C mutation might affect functionality of the transcription factor despite a normal DNA binding, we used a structure modelization approach and also analyzed two other Pit-1 mutant proteins (F135A and F135Y). The loss of functionality in these two mutants was similar to that of F135C. This finding was in keeping with our molecular modeling studies. According to structural data derived from the crystallographic analysis of the DNA/Pit-1 POU domain complex, the conformation of the first helix of the F135C-mutated POU-specific domain could be perturbed to such an extent that any interaction with other transcription cofactors might be definitively prevented.

Amino Acid Sequence↗

Multifactorial control of pituitary hormone secretion: the "wheels" of the brain.

An attempt is made to deal with the complexity of the nerve fibers in the median eminence. Visual aids are presented in the shape of "wheels" that depict a dynamic interplay of neurochemicals which result in the release of hormones from the anterior pituitary gland. The multiplicity of neurochemicals in the median eminence is perceived to be responsible for the integrated control of pituitary hormone releasing factors.

Animals↗

Porphyrin metabolism in the harderian glands of Syrian hamsters: in vivo regulation by testicular hormones, lighting conditions, pineal gland, and pituitary hormones.

The porphyrin concentration in the harderian glands of male hamsters subjected to several endocrine manipulations was studied. Prolonged bilateral gonadectomy resulted in a marked increase in harderian porphyrin concentration. This change was not prevented by either pinealectomy or by constant white light exposure. Castrated hamsters exposed to constant red light showed higher porphyrin concentrations than castrated hamsters kept under white light. Among several hormones studied, serum luteinizing hormone and thyroid-stimulating hormone levels were unexpectedly higher in the constant red light exposed group than in the other groups. In order to test whether luteinizing hormone was involved in the postcastrational rise in harderian porphyrins, we administered a potent luteinizing hormone-releasing hormone (LHRH) agonist. The chronic administration of the LHRH agonist resulted in a decrease in serum luteinizing hormone (because it desensitized the LHRH receptors on the gonadotropes) and, consequently, in serum testosterone levels. However, no rise in harderian porphyrin was observed. It is concluded that the absence of testicular hormones might not be the triggering factor involved in harderian porphyrogenesis.

Animals↗

The combined effect of growth hormone and methandrostenolone on the linear growth of patients with multiple pituitary hormone deficiencies.

Six patients with multiple pituitary hormone deficiencies (MPHD) were initially treated with separate courses of methandrostenolone and growth hormone and later with the two drugs combined. During the basal period the mean growth velocity was 2.8 cm/year. Methandrostenolone alone, 0.02-0.05 mg/kg/day given to four of the patients led to an acceleration of the growth velocity to a mean of 5.0 cm/year, while growth hormone 6 mg/week alone accelerated the growth rate to a mean of 6.0 cm/year. Combined therapy led to a striking increase in the mean growth rate to 9.3 cm/year. The shortcoming of the combined growth hormone-androgen therapy was the fast acceleration in skeletal maturation even after short-term administration.

Adolescent↗

Secretion of anterior pituitary hormones in patients with insulin-dependent diabetes mellitus and polyglandular autoimmune syndrome.

We extracted gammaglobulins from the serum of 10 patients with insulin-dependent diabetes mellitus (IDDM) to investigate their effect on anterior pituitary hormone secretion using cultures of rat anterior pituitary cells. Three of the 10 patients also had the polyglandular autoimmune syndrome (PGA) type III with an isolated failure of anterior pituitary hormone secretion. The gammaglobulin from each of the 3 patients with PGA and an isolated failure of secretion of adrenocorticotropic hormone (ACTH), thyroid stimulating hormone (TSH) or gonadotropin inhibited the secretion of ACTH, TSH or gonadotropin in cultures of rat anterior pituitary cells. The gammaglobulins obtained from the other 7 patients with IDDM also showed an inhibitory or stimulatory effect on anterior pituitary hormone secretion in vitro. We postulate that some patients with IDDM, especially those with other endocrine autoimmune diseases, may have substances in their gammaglobulin fraction that can affect the secretion of anterior pituitary hormones.

Adrenocorticotropic Hormone↗

Interaction of alpha-melanocyte-stimulating hormone with beta-endorphin to influence anterior pituitary hormone secretion in the female rat.

The interaction of alpha MSH and beta-endorphin on the secretion of PRL, GH, and LH was determined in the ovariectomized rat. The potent stimulatory effect on PRL release of injection of 20 ng (5.8 pmol) beta-endorphin into the third cerebral ventricle was completely blocked by 100 ng (60 pmol) alpha MSH. The same dose of alpha MSH partially blocked the effect of 150 ng (44 pmol) beta-endorphin on PRL secretion. Intraventricular injection of either 20 ng beta-endorphin or 100 ng alpha MSH had no effect by itself on plasma LH. However, coinjection of these doses of beta-endorphin and alpha MSH suppressed plasma LH levels significantly within 15 min. beta-Endorphin (150 ng) produced a significant suppression of plasma LH levels. Furthermore, coadministration of 100 ng alpha MSH with 150 ng beta-endorphin lowered plasma LH for a longer period of time than this dose of beta-endorphin alone. Low doses of beta-endorphin (20 ng) or alpha MSH (100 ng) alone or in combination did not alter plasma GH levels. A higher dose of 150 ng beta-endorphin produced a slight elevation of plasma GH. This effect was potentiated 5-fold when 150 ng beta-endorphin were injected in combination with 100 ng alpha MSH. These results indicate that alpha MSH acts as an antagonist to beta-endorphin in regard to the secretion of PRL, whereas it potentiates the effect of beta-endorphin in stimulation of GH and inhibition of LH secretion.

Animals↗

[Determination of pituitary hormones in cerebrospinal fluid in normal subjects and in hypothalamo-pituitary diseases. Secreting or non-secreting pituitary adenoma, empty sella syndrome, hypothalamic syndromes].

Cerebrospinal fluid (CSF) and serum concentrations of TSH, ACTH, FSH, LH, GH and PRL were measured simultaneously in 34 subjects divided into 3 groups: I--12 normal subjects (6 males and 6 females); II--12 prolactin adenomas (3 males and 9 females); III--5 empty sella syndromes; 3 hypothalamic disorders; 1 chromophobe adenoma; 1 pituitary dwarfism. It is concluded that:--pituitary hormones are the normal constituents of CSF but the level can be undetectable and in any case lower than the serum level; --there is a positive correlation between serum and CSF concentration of PRL when serum PRL is higher than 20 ng/ml, indicating that the CSF level is influenced by serum level; --in prolactin adenomas only prolactin is elevated in the CSF; --there is no correlation between the high level of CSF-PRL and a suprasellar extension of the adenoma.

Adenoma↗

Postmortem stability of pituitary hormones in the human adenohypophysis.

The hypophysis is embedded in the fossa at the base of skull, having important functions in the hormonal system. The present study investigated its postmortem morphological changes and the stability of adenohypopyseal hormones. The pituitaries were collected at autopsy 6 h to 20 days postmortem and were studied by histology, immunohistochemistry and electron microscopy. To avoid the influence of prolonged brain hypoxia or swelling, subjects who survived not longer than 12 h were examined. Histological changes were seen in the nucleus 6 h after death, followed by cytoplasmic changes, and the cell shapes were hardly identifiable 7 days postmortem. Electron microscopy revealed evident ultra-structural changes 6 h postmortem, involving rough endoplasmic reticulum, Golgi complexes, mitochondria, nuclei and cell membranes. However, secretory granules remained well preserved 7 days postmortem. Immunostaining showed positivities for growth hormone, prolactin, adenocorticotropic hormone, luteinizing hormone and thyroid-stimulating hormone up to 15 days after death. These findings suggest the usefulness of immunohistochemical investigation of the adenohypophysis for estimating the time of death and endocrinologic evaluation in decomposed cadavers.

Adolescent↗

[Hypothalamic pituitary function in brain death patients--from blood pituitary hormones and hypothalamic hormones].

According to the report of the Health and Welfare Ministry's research committee on brain death (1985), "brain death is defined as an irreversible cessation of the total brain function including brain stem." However, in brain death patients, whether the hypothalamic function which belongs to the brain stem function has completely ceased or not is unknown. In order to evaluate the hypothalamic function in brain death patients, the blood levels of the pituitary hormones and hypothalamic hormones were measured, and anterior pituitary stimulation test with triple bolus injection (TRH 500 micrograms, LH-RH 100 micrograms, regular insulin 0.3-0.7 unit/kg) was performed. The subjects were 13 brain death patients whose clinical states fully satisfied the criteria proposed by the committee. 1) The average blood levels of anterior pituitary hormones in these brain death patients were within normal range, and that of growth hormone was more than the twice of the normal level. 2) The blood anterior pituitary hormones were detectable in almost all cases even several days after the diagnosis of the brain death. 3) LH reserve was maintained in three cases. FSH reserve was maintained in three cases. Prolactin reserve was maintained in two cases. TSH reserve was maintained in one case. 4) Blood ADH (antidiuretic hormones) were detectable in 7 cases out of 9 cases. The blood ADH level of one case, in particular, was rather high (above 10 pg/ml). 5) Histopathologically anterior pituitaries were examined in three autopsy cases. The central necrotic areas were observed in all cases, but normal pituitary tissues existed peripherally. And all anterior pituitary hormones could be recognized immunohistochemically. 6) The blood levels of the hypothalamic hormones (GRF, CRF, LH-RH) were measured in four cases. The hypothalamic hormones were detectable in all cases. In one case, the levels of GRF were within normal range even 9 or 15 days after the diagnosis of brain death.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Divergent influences of calcium ions on releasing factor-stimulated anterior pituitary hormone secretion in normal man.

To investigate the influence of calcium ions on the secretion of anterior pituitary hormones in response to stimulation by exogenous hypothalmic releasing factors in man, we measured serum concentrations of pituitary hormones serially during a continuous infusion of combined TRH (2 micrograms/min) and GnRH (1 microgram/min), with concomitant iv saline or calcium administration. Compared to saline, calcium administration was associated with a significant increase in GnRH-TRH-stimulated LH and FSH release and a corresponding rise in serum testosterone concentrations. The effect of calcium ions on gonadotropin secretion was specific, because releasing factor-stimulated secretion of TSH and PRL was suppressed by hypercalcemia. Serum concentrations of GH were not significantly altered under these conditions. In summary, the present results provide the first in vivo evidence that acute infusion of calcium ions augments GnRH-TRH-stimulated secretion of LH and FSH, with an accompanying increase in serum testosterone levels. In contrast, hypercalcemia did not alter serum GH concentrations, and it suppressed GnRH-TRH-stimulated release of PRL and TSH. We conclude that calcium ions can selectively influence releasing factor-stimulated secretion of certain anterior pituitary hormones in man.

Adult↗

Vitellogenin hormonal control in the green frog, Rana esculenta. Interplay between estradiol and pituitary hormones.

1. The effect of estradiol and pituitary hormones on the titre of serum vitellogenin has been studied in Rana esculenta by rocket immunoelectrophoresis. 2. Hepatic synthesis of vitellogenin depends on physiological doses of estradiol. 3. Gonadotrophins enhance the uptake, presumably by acting directly on the oocyte plasma membrane. 4. In addition, our data support direct pituitary intervention on liver synthesis and/or release of vitellogenin. 5. Hormonal response, as evaluated by vitellogenin serum titres, tends to increase from November to July. This could be the expression of a modification, throughout the sexual cycle, of liver sensitivity to the hormones.

Animals↗

Importance of pituitary hormones in aetiology of diabetic ketoacidosis.

The role of pituitary hormones in the aetiology of diabetic ketoacidosis was examined by withdrawing insulin from five pituitary-ablated diabetics for a 12-hour period. The rise in blood glucose and ketone-body concentrations was markedly retarded in these patients when compared with five matched juvenile-type diabetic controls with normal pituitary function. When cortisol replacement in the pituitary-ablated patients was increased to reproduce the high plasma concentrations found in severe ketoacidosis, blood ketones and glucose were increased but were still significantly lower than in the control diabetics. It is concluded that pituitary hormones may be important in the development of diabetic ketoacidosis.

Adult↗

Cadmium effects on hypothalamic activity and pituitary hormone secretion in the male.

Cadmium specifically modify amine metabolism at the central nervous system and pituitary hormone secretions. Thus, the physiological functions controlled by these hormones can be modulated by cadmium. This xenobiotic is associated with deleterious effects on the gonadal function and with changes in the secretory pattern of other pituitary hormones like prolactin, ACTH, GH or TSH. The observed changes in pituitary hormone secretion do not correlate with the modifications of central nervous system metabolism of the neurotransmitters involved in their regulation. The accumulative data indicates the existence of a disruption in the regulatory mechanisms of the hypothalamic-pituitary axis. The physiological significance of these effects remains to be elucidated.

Adrenocorticotropic Hormone↗