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The role of histamine in the neuroendocrine regulation of pituitary hormone secretion.

The neurotransmitter histamine participates in the neuroendocrine regulation of pituitary hormone secretion by an indirect action at a hypothalamic level where histaminergic neurons are abundant. The effect of histamine is caused by activation of postsynaptic H1- or H2-receptors. Histamine stimulates the secretion of ACTH, beta-endorphin (mediated by CRH and AVP), alpha-MSH (mediated by dopamine and peripheral catecholamines), and PRL (mediated by dopamine, serotonin and AVP), and participates in the stress-induced release of these hormones and possibly in the suckling- and estrogen-induced PRL release. The release of GH and TSH is predominantly inhibited by histamine; however, uncertainty exists regarding its role and the hypothalamic factors involved. Histamine increases the secretion of LH in females (mediated by GnRH), and may be involved in the mediation of the estrogen-induced LH surge. AVP and oxytocin are stimulated by histamine, probably by an effect in the supraoptic and paraventricular nuclei of the hypothalamus.

Animals↗

1,25-dihydroxyvitamin D3-mediated transforming growth factor-beta release is impaired in cultured osteoblasts from patients with multiple pituitary hormone deficiencies.

To evaluate the osteoblastic function in patients with multiple pituitary hormone deficiencies (M-PHD) and with isolated growth hormone deficiency (I-GHD), bone cells were cultured and the effects of 10(-8) M 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) on parameters of cell proliferation, osteoblastic differentiation, and local paracrine regulation were measured. Three days of 1,25(OH)2D3 treatment increased alkaline phosphatase activity and osteocalcin release but inhibited [3H]thymidine incorporation in all cell cultures from patients as well as from controls. In addition, 1,25(OH)2D3 increased the release of both total and active transforming growth factor-beta (TGF-beta) in bone cells from controls by, respectively, 4.9- and 3.2-fold and in bone cells from I-GHD by 5.1- and 1.5-fold, respectively. However, in bone cells from M-PHD, the stimulation of total TGF-beta release was significantly lower (1.3-fold) than in control and I-GHD cells, and active TGF-beta release was not stimulated at all. One year of supplementation with human growth hormone did not improve this deficient TGF-beta release in bone cells from M-PHD. We conclude that cultured bone cells from I-GHD and M-PHD show a normal response to 1,25(OH)2D3 regarding cell proliferation and osteoblastic differentiation, which implicates a normal 1,25(OH)2D3-receptor function. In cells from controls and I-GHD, 1,25(OH)2D3 enhanced both total and active TGF-beta release. However, bone cells from M-PHD showed a deficient TGF-beta response to 1,25(OH)2D3. These results suggest that the regulation of TGF-beta production is a major paracrine factor involved in hypopituitarism.

Adult↗

Pituitary hormones and the small bowel: effect of hypophysectomy on intestinal adaptation to small bowel resection in the rat.

The influence of pituitary hormones on intestinal adaptation to small bowel resection was studied by examining jejunal and ileal structure and function in control and in sham-operated rats, and in animals with 50% proximal or distal resection which were divided into three main groups: normally-fed, hypophysectomized. and pair-fed. The pituitary was removed 2 weeks before intestinal surgery and gut structure and function were studied 4 weeks later. The effectiveness of hypophysectomy was confirmed by histological examination of the aspirated pituitary, and by showing a significant subsequent reduction in weight of the testes and adrenals. Food intake and body weight fell significantly after removing the pituitary; intestinal surgery caused a transient further decrease in food intake. Measurements of intestinal villus height and crypt depth, indices of mucosal mass (mucosal wet weight, protein and DNA content/cm intestine), measurements of mucosal alpha-glucosidase activity, and in vivo galactose absorption/unit length of intestine all showed comparable results. In rats with an intact intestine, resection resulted in mucosal hyperplasia and increased segmental absorption. Following hypophysectomy, there was marked mucosal hypoplasia and hypofunction which seemed to be due largely to associated hypophagia since comparable changes were found in the pair-fed, sham-operated rats. However following pituitary removal, both distal jejunum and proximal ileum retained their capacity to regenerate though the magnitude of this adaptive change was much greater in the resected, pair-fed rats suggesting that hypophagia alone cannot explain the diminished adaptation to resection after hypophysectomy. By inference, pituitary hormones do influence the adaptive response to resection.

Adaptation, Physiological↗

Recently discovered hypothalamic-pituitary hormones.

In recent years a variety of peptide hormones have been isolated from the mammalian hypothalamus and pituitary. Several hypothalamic hormones, including thyroliberin (thyrotropin-releasing factory), luliberin (luteinizing hormone-releasing factor), and somatostatin (somatotropin release-inhibiting factor), have been characterized and synthesized. The subsequent development of radioimmunoassays for these hormones has made possible the study of their physiology. The measurement of prolactin in serum and the release of pituitary hormones after the administration of the hypothalamic hormones has proved to be useful in clinical diagnosis. The use of hypothalamic hormones in treating various clinical disorders and the isolation and characterization of new releasing and inhibiting hormones in the hypothalamus are actively being investigated.

Acromegaly↗

Suppression of levels of phenobarbital-inducible rat liver cytochrome P-450 by pituitary hormone.

The effect of pituitary factor on the constitutive and inducible levels of hepatic phenobarbital (PB)-inducible major cytochrome P-450, P-450b and P-450e, in male and female rat livers was studied by immunoblot analyses. Although only trace amounts (approximately 4 pmol/mg protein) of P-450b and P-450e were detected in untreated adult rats, hypophysectomy increased the contents of P-450b and P-450e 58- and 14-fold, respectively, in male rats and 118- and 30-fold, respectively, in female rats. The increases were also observed in treatment with dexamethasone, which suppressed the pituitary function. Treatment with PB increased more effectively the hepatic contents of P-450b and P-450e, but their contents were still 4-fold higher in the male than the female. Treatment of hypophysectomized female rats with PB increased the contents of P-450b and P-450e 4-fold higher than the contents in PB-treated nonhypophysectomized female rats. Consequently, the sex-related difference in their contents was reduced less than 1.4-fold in the hypophysectomized rats treated with PB. Similar results were also obtained from the quantitation of microsomal O-pentylresorufin O-depentylation and testosterone 16 beta-hydroxylation. Either intermittent injection or continuous infusion of human growth hormone, but not of ovine prolactin, into hypophysectomized male and female rats decreased the contents of both cytochromes. These results indicate that growth hormone acts as a repressive factor for the constitutive and inducible levels of P-450b and P-450e in a manner different from the regulation of P-450-male and P-450-female.

Aging↗

Relationship between pituitary hormones, antioxidant enzymes, and histopathological changes in the mammary gland of senescent rats.

In order to assess the possible involvement of endocrine factors and antioxidant enzymes (AOE) in the mammary pathology typically observed in old female rats, we undertook to determine the relationship between pituitary hormones, AOE activity, and histopathological changes in the mammary gland of senescent rats carrying neoplastic and nonneoplastic mammary pathologies. Serum levels of several pituitary hormones were determined by RIA in young (five months) and senescent (33 months) Sprague-Dawley female rats. The activity of catalase (CAT) and superoxide dismutase (SOD) in mammary tissue from the senescent animals was also determined. Senescent rats showed higher levels of prolactin (PRL) (p < 0.01), thyroid-stimulating hormone (TSH) (p < 0.05) and follicle-stimulating hormone (FSH) (p < 0.01) than their young counterparts. In senescent females the main histopathological findings at mammary level were a marked hyperplasia and the presence of fibroadenomas. In this group there was a positive correlation between serum levels of PRL and the activity of mammary SOD (p < 0.05). There was also a positive correlation between serum levels of FSH and the activity of mammary CAT (p < 0.001). Young females, rendered moderately hyperprolactinemic by means of anterior pituitary grafts, showed clear proliferative changes in their mammary glands. Senescent rats carrying fibroadenomas were less hyperprolactinemic than those with mammary hyperplasia (p < 0.05). Our results provide additional support to the idea that PRL may be a physiological modulator of mammary SOD activity and suggest that FSH can possibly influence the activity of CAT in mammary gland. They also suggest that tumorigenesis but not hyperplasia in rat mammary gland may be associated with low mammary SOD and CAT activities.

Aging↗

Pituitary hormone response to head injury.

Measurements of the serum levels of pituitary hormones were made in six patients with uncomplicated head injury. Samples were obtained at 4-hour intervals for 72 hours to evaluate diurnal rhythms. Three of the six patients revealed elevations of serum growth hormone (GH) and prolactin, but no trends could be established. Likewise, three patients had marked elevations of luteinizing hormone and lesser elevations of follicle-stimulating hormone, but no pattern was discernible. The level of thyroid-stimulating hormone was stable and remained in the normal range throughout. GH was measured after intravenous glucose loading. A paradoxical rise reverted to normal at the late follow-up evaluation. It is suggested that the abnormal levels were related to abnormal hypothalamic function rather than to pituitary damage.

Adolescent↗

Pituitary hormones dependent expression of insulin-like growth factors I and II in the immature hypophysectomized rat testis.

Since insulin-like growth factors I (IGF-I) and II (IGF-II) appeared involved in paracrine or autocrine regulation of both cell multiplication and differentiation of the rat testis, we have investigated the pituitary hormonal dependence of IGF-I and IGF-II mRNA production in the testis of immature hypophysectomized rats (22 days old) supplemented with highly purified FSH, LH, GH or PRL. Our data show that testicular expression of IGF-I mRNA as measured by dot-blot hybridization, is increased by LH, FSH or GH treatments of 7-, 6-, and 4-fold, respectively, above controls. Intensity of the signal was 3-fold lower after PRL treatment than in hypophysectomized control rats. On the contrary, IGF-II mRNA expression, was found low in the immature hypophysectomized rat testis and unmodified by any hormonal treatment. In contrast to the increase of IGF-I expression in the testis no significant change in the IGF-I plasma concentration was observed after LH or FSH supplementation. GH treatment, as expected, increased 4-fold the IGF-I plasma concentration of the experimental animals. Since we have previously shown that LH, FSH, and GH exhibit selective cell multiplication and differentiation in the testis of our animal model, it is proposed that testicular IGF-I expression could be the tissue response to pituitary hormone in these phenomena.

Animals↗

Altered specificity of the blood-cerebrospinal fluid barrier for pituitary hormones in patients with tumoral hypothalamo-hypophyseal diseases as proved by releasing hormones stimulation.

Growth hormone (GH), prolactin (PRL) and gonadotropins (LH and FSH) of cerebrospinal fluid (CSF) and serum were radioimmunologically measured in basal condition in 75 cases and during the stimulation with releasing hormones in 24 of cases, i.e. with TRH plus LRH i.v. Samples were obtained from 75 patients of the following groups: A. control group of 9 patients without endocrine diseases; B. 8 patients with nontumoral diseases, of whom 4 with organic cranial diabetes insipidus and 4 with empty sella syndromes; C. 36 patients with invasive tumors i.e. 6 hypothalamic metastatic carcinomas and 300 invasive pituitary adenomas; D. 22 patients with enclosed tumors, i.e. 1 suprasellar dermoid cyst and 21 enclosed pituitary adenomas. Minimum 3 pituitary hormones were measured in each analyzed sample, and only those hormones, not secreted by the tumoral cells, were analyzed for their differential penetration into the CSF. An increase of the permeability of the blood-CSF barrier (BCB) was frequently observed in the group of invasive tumors and occasionally in the other tumoral or non-tumoral groups. The serum/CSF ratios of gonadotropins become significantly lower than the ratios of GH and PRL in the invasive groups (p less than 0.02), and here the CSF level was correlated to the increases of the serum levels during LRH plus TRH i.v. test only for gonadotropins. These data suggest that the specificity of BCB is not lost, but altered by the tumors of the hypothalamo-hypophyseal region, with an increase of the permeability for gonadotropins more than for GH or PRL.

Adult↗

Anterior pituitary hormone levels in the cerebrospinal fluid of patients with pituitary and parasellar tumors.

Cerebrospinal fluid (CSF) concentrations of growth hormone, prolactin (PRL), adrenocorticotropin, thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing hormone, and the glycoprotein hormone alpha subunit were determined in 30 patients with pituitary and parasellar tumors. Although many of the patients had elevated hormone levels, no differentiation between patients with intrasellar tumors and those with pituitary tumors with suprasellar extension or primary suprasellar tumors could be made based upon the absolute CSF hormone concentration. A highly significant correlation between serum and CSF PRL concentrations was found (r = 0.87; P less than 0.001), suggesting that CSF PRL is derived from the serum. No correlation was found between the serum and CSF concentrations of the other anterior pituitary hormones.

Adrenocorticotropic Hormone↗

Anabolic effect of prostaglandin E2 in bone is not dependent on pituitary hormones in rats.

Prostaglandin E2 (PGE2) is an anabolic agent of bone in vivo but the mechanism of its action still remains unclear. The aim of this study was to determine whether the effect of PGE2 on skeleton is mediated by pituitary hormones. Forty female, Sprague-Dawley rats were divided into four groups: baseline control (basal), age-matched intact control (CON), hypophysectomy (HX), and HX + PGE2 (2 mg/kg/day) with 10 animals in each group. The basal group was sacrificed at 2 months of age, and the remaining groups after 6 weeks of treatment. Cancellous and cortical bone histomorphometry was performed on double fluorescent-labeled 40 micron-thick sections of the proximal tibia and tibial shaft. Our results show that HX resulted in a cessation of bone growth, a decrease in cancellous bone volume, and cortical bone gain compared with the age-matched, intact CON rats. Compared with the HX group, the HX + PGE2 group had a significantly greater tibial bone density (mean +/- SE, HX + PGE2:1.595 +/- 0.007 versus HX:1.545 +/- 0.013), percent cancellous bone volume (21.4 +/- 2.0 versus 8.41 +/- 1.70), percent cortical bone area (87.2 +/- 0.85 versus 81.7 +/- 0.7), and ratio of cortical area to marrow area (7.14 +/- 0.56 versus 4.52 +/- 0.21). Increased bone masses by PGE2 in the HX animals were accompanied by an increase in the trabecular and endosteal-labeled surface and bone formation rate. The trabecular number and width were increased whereas trabecular separation was decreased in the HX + PGE2 group compared with the HX group (P < 0.05). PGE2 treatment also caused a decrease in the tibial endosteal eroded surface and medullar cavity of the HX animals. In conclusion, this study clearly demonstrates that PGE2 (2 mg/kg/day) in the HX rats increases both cortical and cancellous bones and improves trabecular architecture in the tibia after 6 weeks of treatment. These skeletal alterations are due to a stimulation of bone formation and a suppression of bone resorption activity. These findings suggest that the anabolic effect of PGE2 in bone is independent of pituitary hormones.

Animals↗

Salient characteristics of bovine pituitary intraglandular colloid: a transport medium for determinants to pituitary hormones and immunoglobulins.

Bovine hypophyseal intraglandular colloid, the holocrine secretion of marginal intermediate lobe cells, contains high molecular weight (MW 45 000 to 158 000) protein fractions and low molecular weight (MW below 25 000) peptide fractions. The fractions display immunoreactive determinants similar to those in pituitary hormones, cerebrospinal fluid (CSF), serum IgG and albumin. Immunoelectrophoresis shows that components in high molecular weight fractions distribute themselves in three distinct bands (gamma, beta, alpha), while those in low molecular weight fractions distribute themselves in two bands (gamma and alpha). Physiochemical characteristics, i.e., sedimentation rate, percentage of hexose, total CHO and 12C as well as the content of cystine are presented. It is concluded that pituitary colloid should not be dismissed as a waste product of cellular degeneration, since there are strong suggestions that it serves as a transport medium for certain pituitary hormones.

Albumins↗

Could craniopharyngiomas produce pituitary hormones?

The authors have studied the endocrinological characteristics of 13 craniopharyngioma biopsy specimens in paraffin embedded histological sections with immunohistochemical methods for pituitary hormones (GH, PRL, ACTH, TSH, FSH and LH). Scattered cell groups with mild to moderate positivity for at least one hormone were found in all but one case. This finding supplies further evidence to the hypothesis which suggests the Rathke's pouch origin of craniopharyngiomas. Beside the hypothalamic-hypophyseal lesion it might explain the endocrinological disturbances accompanying the patients suffering from these tumours.

Craniopharyngioma↗

Interaction between morphine, an opioid agonist, and clonidine, an alpha-adrenergic agonist, on the regulation of anterior pituitary hormone secretion in normal male subjects.

In order to investigate the possible interaction between opioid system and noradrenergic system in the regulation of pituitary hormone secretion, the effects of morphine (an opioid agonist, 10 mg i. v.), clonidine (an alpha-adrenergic agonist, infusion of 0.3 mg in 15 minutes) and clonidine + morphine (infusion of the same dose of clonidine beginning 30 minutes before morphine 10 mg i.v.) on anterior pituitary hormone secretion were studied in six normal male volunteers. Morphine alone induced both an increase in TSH and PRL serum levels and a decrease in cortisol serum levels with no changes in GH serum levels. On the contrary clonidine was able to increase GH and TSH levels and to decrease cortisol levels; PRL secretion was not affected. As regards interaction between morphine and clonidine we observed that morphine-induced increase in PRL release was potentiated by clonidine pretreatment; as regards TSH secretion its increase was greater after the administration of the two drugs with respect to the effect of the single drugs. This study, in agreement with our previous data concerning LH secretion, confirms the important link between clonidine and opioid system in neuroendocrine function, too; the possible explanations of our data are discussed.

Adult↗

Dose effects of recombinant human interleukin-6 on pituitary hormone secretion and energy expenditure.

Interleukin-6 (IL-6), the main circulating cytokine, is putatively a major mediator of the effects of the immune system on several endocrine axes and intermediate metabolism. We performed dose-response studies of recombinant human IL-6 on pituitary hormone secretion in 15 healthy male volunteers, using 5 single, escalating subcutaneous doses of IL-6 (0.1, 0.3, 1.0, 3.0 and 10.0 micrograms/kg body weight), each in 3 volunteers. We measured resting metabolic rate (RMR) with indirect calorimetry and plasma anterior pituitary hormones and vasopressin (AVP) at baseline and half-hourly over 4 h after the injection. All doses examined were tolerated well and produced no significant adverse effects. Dose-dependent RMR increases were observed in response to the 3.0- and 10.0-microgram/kg doses of IL-6, beginning at 60 min and slowly peaking between 180 and 240 min. Plasma adrenocorticotropic-hormone concentrations increased dramatically and dose-dependently in all the patients who received the 3.0- and 10.0-microgram/kg doses of IL-6, respectively, peaking to 150 and 255 pg/ml at 60 min, and slowly returning to normal by 4 h. Corresponding plasma cortisol levels peaked dose-dependently between 90 and 150 min, but remained elevated throughout the sampling period. In contrast, the growth hormone (GH) dose-response was bell-shaped, with maximum (approximately 100-fold) stimulation achieved by 3.0 micrograms/kg IL-6. Prolactin (PRL) showed a similar but less pronounced response pattern. Thyroid-stimulating hormone (TSH) dose-dependently and progressively decreased over the 240 min, while gonadotropins showed no clear-cut changes. In conclusion, subcutaneous IL-6 administration induced synchronized dose-dependent increases in the RMR and hypothalamic-pituitary-adrenal axis activity, suggesting that hypothalamic corticotropin-releasing hormone may mediate both of these functions in humans. IL-6 also acutely stimulated GH and PRL secretion and suppressed TSH secretion. The dose of 3.0 micrograms/kg could be used safely in the study of patients with disturbances of the hypothalamic-pituitary unit or of thermogenesis.

Adrenocorticotropic Hormone↗

Regulation of galanin-like peptide gene expression by pituitary hormones and their downstream targets.

Galanin-like peptide (GALP) mRNA is expressed in neurones of the hypothalamic arcuate nucleus and within pituicytes in the neurohypophysis. Several neuropeptides that are expressed in the arcuate nucleus participate in the neuroendocrine regulation of pituitary hormone secretion. Our objective was to determine the extent to which GALP might be a target for regulation by pituitary hormones or their downstream targets in the rat. The expression of GALP mRNA in the arcuate nucleus was reduced by hypophysectomy as determined by in situ hybridization. However, this did not appear to be attributable to the loss of either gonadal or adrenal steroids because castrated, ovariectomized and adrenalectomized rats had GALP mRNA expression that was indistinguishable from their respective controls. Next, we investigated the effects of growth hormone deficiency on GALP mRNA expression by studying dwarf rats and found that GALP gene expression was not different between dwarf rats and controls. We found that thyroidectomy led to a significant reduction in GALP mRNA expression compared to intact controls, and thyroidectomized rats implanted with thyroxine pellets had GALP mRNA expression that was similar to intact controls. Thus, the reduction of GALP mRNA expression seen in hypophysectomized animals may reflect, in part, a selective loss of thyroid hormone. We also found that the expression of GALP mRNA was increased in the neurohypophysis of lactating rats compared to nonlactating rats, whereas GALP mRNA expression in the arcuate nucleus was unaffected by lactation. This suggests that the induction of GALP gene expression in pituicytes is physiologically associated with activation of oxytocin and vasopressin secretion during lactation.

Adrenalectomy↗