Further arguments for a functional difference between pituitary corticotroph macroadenomas and microadenomas.
Explore the source record for details and available documents.
17-Hydroxycorticosteroids↗
Biomedical subjects
D M Maiter
Publications and source records attributed to D M Maiter.
Pre- and peroperative misdiagnosed sellar tumour.
We describe the case of a 76-year old woman complaining of headaches and progressive sight loss. Cerebral CT scan and MRI disclosed a large sellar tumour. Endocrine evaluation showed no evidence of pituitary hypersecretion, but a slight hyperprolactinemia related to stalk compression. A non-functioning pituitary adenoma was suspected. The pathological diagnosis was however a meningioma. In the literature, about 5% of sellar tumours are not pituitary adenomas and this is an alternate diagnosis to consider in the presence of non-secreting macroadenomas.
Adenoma↗
Cyclic feeding behaviour and changes in hypothalamic galanin and neuropeptide Y gene expression induced by zinc deficiency in the rat.
Dietary zinc-deficiency induces a striking reduction and a cyclic pattern of food intake in rodents. To elucidate the mechanisms for these effects, we studied the hypothalamic content, synthesis, and distribution of galanin (GAL) and neuropeptide Y (NPY) during zinc deficiency and refeeding in the rat. In Wistar rats, three weeks of zinc-deprivation consistently induced a reduction and a cyclic pattern of night- and day-time food intake, as well as of water intake. This was accompanied in zinc-deficient (ZD) rats, and to a lesser extent in pair-fed (PF) rats, by a decrease of hypothalamic GAL mRNA concentration (CTR: 100 +/- 8, ZD: 61 +/- 4, PF: 78 +/- 2 arbitrary densitometric units, ADU, P < 0.01) and an increase of hypothalamic NPY (CTR: 100 +/- 11, ZD: 154 +/- 10, PF: 126 +/- 4 ADU, P < 0.05), without peptide modification. The two neuropeptidergic systems were not affected by the cycles of feeding, with the exception of the NPY-immunoreactivity in the suprachiasmatic nuclei (geniculo-hypothalamic tract), that was inversely correlated to the food intake in both ZD and PF animals. In a second experiment, we showed that zinc-repletion for 4 days suppressed the behaviour induced by a two-week zinc-deprivation, and reversed the increase of NPY mRNA in ZD animals. We finally demonstrated that zinc-deficiency induced a similar behaviour in Zucker rats. However, in these rats whose synthesis of NPY is constitutively up-regulated, no change of NPY synthesis was observed in ZD rats, suggesting that the increase observed in Wistar is adaptative rather than instrumental to the abnormal food intake. In conclusion, we have further characterized the cyclic feeding behaviour of the zinc-deficient Wistar rats, and shown in these animals a decreased activity of the GAL system and an increased activity of the NPY system, likely corresponding to a compensatory response of the two neuropeptidergic systems, as observed in food-deprived animals. As spontaneous food intake of ZD rats does not increase, a resistance to NPY could also be present. These behavioural and neuropeptidergic changes were partially reversed by reintroduction of zinc in the diet. In Zucker rats, the same behaviour occurred despite an insensitivity of the NPY system to the zinc-deficiency. In addition, we describe a nutritional regulation of the NPY-immunoreactivity in the geniculo-hypothalamic tract, that could constitute the substrate of circadian rhythm modulation by timed feeding.
Aging↗
A novel transcriptional activator originating from an upstream promoter in human growth hormone gene.
Transcription of the human growth hormone gene can start in vitro and in vivo 197 base pairs upstream from the cap site of growth hormone mRNA (Courtois, S. J., Lafontaine, D., and Rousseau, G. G. (1992) J. Biol. Chem. 267, 19736-19743). We have now characterized the mRNA that originates from this optional promoter and have found that it occurs in human hypophysis and placenta but not in 10 other tissues. This mRNA contains an open reading frame for a protein of 107 residues that shares sequence similarity with three domains of hepatic nuclear factor-1alpha. With antibodies directed against a peptide corresponding to the C terminus of this protein, immunoreactive material was detected in a subset of cells of the adenohypophysis. When fused to the DNA-binding domain of the yeast transcription factor GAL4, the protein stimulated transcription from a GAL4-sensitive reporter gene in transiently transfected pituitary and placental cells.
Amino Acid Sequence↗
Dietary protein restriction inhibits growth hormone-induced DNA synthesis without impairing c-myc and c-Ha-ras expression in the liver of hypophysectomized rats.
Cellular proliferation is impaired by malnutrition, and the mechanisms responsible for this inhibitory effect are poorly understood. One possible mechanism might involve alterations of the cell cycle-associated proto-oncogene expression. To test this hypothesis, we studied the effects of dietary protein restriction on DNA synthesis and c-myc and c-Ha-ras proto-oncogene mRNA responses to growth hormone in the liver of hypophysectomized rats. In rats fed a normal protein diet (15% protein), growth hormone injection induced a sequential activation of c-myc expression (13 times the baseline value, after 1 h) and c-Ha-ras expression (two times the baseline value, after 6 h), which was followed by a stimulation of liver DNA synthesis (9 times the baseline value, after 24 and 36 h). In rats fed a protein-restricted diet (5% protein), growth hormone injection did not induce liver DNA synthesis after 24 or 36 h. However, the baseline level of c-myc mRNA was higher in protein-restricted than in rats fed a normal diet and that of c-Ha-ras mRNA was unaffected by protein restriction. Furthermore, the peak response of c-myc mRNA was more important in protein-restricted rats than in rats fed a normal diet, and the c-Ha-ras mRNA response to growth hormone injection was similar in both dietary groups. These results show that dietary protein restriction inhibits growth hormone-induced DNA synthesis without impairing c-myc and c-Ha-ras activation in the liver of hypophysectomized rats.
Animals↗
Sex-steroid control of galanin in the rat hypothalamic-pituitary axis.
To further investigate how sex steroids regulate galanin (GAL) in the rat pituitary and hypothalamus, we examined the effects of prepubertal gonadectomy (Gx) and long-term (9 weeks) replacement with estradiol (E2) or testosterone (T) on pituitary and hypothalamic GAL concentrations in Wistar rats (5-6/group). Sham-operated animals served as controls (CTR). Pituitary GAL concentration was markedly higher in random-cycling CTR-females than in CTR-males (1391 +/- 247 vs 39 +/- 5 pg/mg protein, P < 0.01) and decreased after Gx only in females (20 +/- 3 pg/mg protein, P < 0.01). E2 strongly increased pituitary GAL in Gx-females and Gx-males (4470 +/- 365 and 3853 +/- 347 pg/mg protein, P < 0.01), whereas T had no effect. Inversely, hypothalamic GAL was higher in CTR males than in CTR females (5.4 +/- 0.3 vs 4.0 +/- 0.5 ng/mg protein, P < 0.05), and decreased significantly after gonadectomy in males (3.7 +/- 0.2 ng/mg protein, P < 0.01). The only steroid treatment that significantly modified hypothalamic GAL in Gx animals was administration of E2 to females (5.7 +/- 0.4 ng/mg protein, P < 0.01 vs non-treated Gx). We also studied in hypophysectomized (Hx) rats (8/group) the effects of sex steroids on hypothalamic GAL concentration and distribution. The low hypothalamic GAL concentration observed in male and female Hx rats (1.0 +/- 0.1 ng/mg protein) was significantly increased by T in males and in females (respectively, by 40% and by 50%, P < 0.02) and by E2 in males (by 60%, P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Expression of nitric oxide synthase isoforms in the thyroid gland: evidence for a role of nitric oxide in vascular control during goiter formation.
The thyroid gland is a highly vascular tissue, and its blood flow changes dramatically in various pathological conditions. Although the mechanisms regulating these changes in vascularity and blood flow are not well understood, candidate mediators include endothelin-1 (ET-1) and nitric oxide (NO). In the present study, we used a reverse transcriptase-polymerase chain reaction assay to determine which components of these vasoregulatory pathways are present in the thyroid and to analyze changes in gene expression in an experimental model of goiter formation and involution. Expression of messenger RNAs (mRNAs) encoding ET-1, ET receptors (ETA and ETB), ET-converting enzyme, and the three nitric oxide synthase (NOS) isoforms (NOS I, NOS II, and NOS III) was readily detected in the rat thyroid. After goiter formation was induced by thiouracil and a low iodine diet, there was increased expression of the genes encoding ET-related proteins (ET-1, 3.2-fold; ETA, 2.9-fold; ETB, 3.5-fold) as well as two of the three NOS isoforms (NOS I, 2.7-fold; NOS III, 4.9-fold). During iodide-induced involution, the ET-related mRNA levels remained elevated, whereas those of the two NOS isoforms returned to basal values. ET-converting enzyme, NOS II, and thyroglobulin mRNAs were minimally affected in this model, providing evidence for selective regulation of these genes. To assess whether NO plays a role in vascular changes during goiter formation, animals were treated with a NOS inhibitor, N-nitro-L-arginine methyl ester (NAME). NOS activity in the thyroid was inhibited by more than 75% after treatment with NAME. Thyroid hormone and TSH levels were unchanged. Although NAME had little effect on overall thyroid size, vascular expansion during goiter formation was decreased by 36%. We conclude that the thyroid gland expresses a complex network of vasoactive genes whose expression is regulated dynamically during thyroid goiter formation and involution. NO production and probably other locally produced vasoactive substances are involved in changes in thyroid vascularization.
Animals↗
Pituitary-dependent hormonal regulation of galaninergic neurons in the rat hypothalamus.
To investigate whether pituitary-dependent hormones may regulate galanin (GAL) content, synthesis and distribution in the hypothalamus, female hypophysectomized Wistar rats were treated for 2 weeks with subcutaneous injections of thyroxine (T4, 2 x 1 microgram), bovine growth hormone (GH, 2 x 125 micrograms), cortisol (C, 50 micrograms), subcutaneous implants of beta-estradiol (E2, 5-mm implant, dilution 1:1), or with the combinations [T4+GH], [T4+GH+C+E2] or [T4+GH+C+E2 + rat PRL, 2 x 125 micrograms] (doses/100 g BW/day). Concentrations of GAL in the hypothalamus were measured by radioimmunoassay (RIA) and GAL mRNA abundance was quantified by Northern blot (6 rats/group); 2 rats/group were used for immunohistochemistry. Hypophysectomy caused decreases of hypothalamic GAL peptide and mRNA concentrations (by 70 and 50%, respectively; p < 0.05 vs. intact rats). GAL immunoreactivity disappeared in the median eminence (ME), but increased in the neurohypophyseal magnocellular neurons of hypophysectomized rats. Substitution with T4, GH, [T4+GH], C or E2 had no significant effect on total hypothalamic GAL peptide and GAL mRNA concentrations. A treatment combining [T4+GH+C+E2] increased hypothalamic GAL (1.9 +/- 0.1 vs. 1.2 +/- 0.1 ng/mg protein in untreated hypophysectomized rats; p < 0.01) and GAL mRNA concentrations (127 +/- 19 vs. 59 +/- 2 densitometric units in untreated rats, p < 0.001). Addition of PRL to this combined treatment had no further effect. Treatment with T4, GH, [T4+GH] or E2 enhanced GAL labeling in the ME of hypophysectomized rats. The effect of estrogens was restricted to the GnRH-rich lateral regions of the ME. The combined treatment with [T4+GH+C+E2] restored the ME GAL immunoreactivity to levels observed in intact rats. In contrast, the increased GAL labeling observed in magnocellular neurons after hypophysectomy was not influenced by any hormonal treatment. In conclusion, hypophysectomy leads to marked reductions of hypothalamic GAL and GAL mRNA concentrations, and of GAL immunoreactivity in the ME. These reductions are prevented in part by a combined hormonal treatment associating T4, GH, C and E2, but not by any hormone given alone. This suggests specific pituitary hormone-dependent regulation of the hypophysiotropic GAL neurons. In contrast, the increased GAL labeling in magnocellular neurons of hypophysectomized rats persists despite hormonal treatment and likely represents a lesional effect on the neurohypophyseal GAL system.
Animals↗
Expression of the endothelin-1 gene in the rat thyroid gland and changes in its peptide and mRNA levels in goiter formation and iodide-induced involution.
Endothelin-1 (ET-1) is a major vasoconstrictor peptide, first found in endothelial cells, and later in many other tissues, including the thyroid gland. We analysed the expression of the ET-1 gene in the rat thyroid gland and changes in ET-1 mRNA and peptide levels in goiter development and involution, two circumstances characterised by vascular changes. Thyroid hyperplasia was induced in adult Wistar rats by feeding a low iodine diet (LID) supplemented with 0.25% thiouracil for 10 days, and LID alone for 2 further days (H.12 group). Involution was induced by injecting 100 micrograms iodide and refeeding a normal diet during 6 h, 12 h, and 24 h (I.6h, I.12h, I.24h groups). Rats fed a normal iodine diet were used as controls. A specific 488 bp cDNA corresponding to the known sequence of pre-pro ET-1 was found by RT-PCR from RNA extracts in all thyroid experimental groups, as well as in lung and kidney which were used as positive controls. RP-HPLC analysis showed that ET-1 immunoreactivity eluted similarly as mature ET-1. During hyperplasia, ET-1 mRNA and peptide levels were increased 3.5- and 5-fold respectively. The relative volume of the vascular bed was more than doubled. During iodide-induced involution, the glandular ET-1 mRNA level remained elevated. The concentration of ET-1 peptide increased and was significantly greater at 12 h involution than in the H.12 group. At this time, the capillary reticulum reverted to individual capillaries and the vascular bed was significantly reduced. These data demonstrate that the ET-1 gene is expressed in the rat thyroid gland and that the ET-1 mRNA and peptide levels are increased during thyroid hyperplasia and remain elevated during a phase of rapid iodide-induced involution. These data suggest that changes in ET-1 production may play a role in control of thyroid gland trophic regulation and vascularity.
Animals↗
Effects of hypophysectomy on galaninergic neurons in the rat hypothalamus.
To understand better the relationship between hypothalamic galaninergic neurons and the pituitary gland, we studied the effects of hypophysectomy on hypothalamic galanin (GAL) content and distribution by radioimmunoassay and immunohistochemistry, and on GAL mRNA by Northern blot analysis. Three weeks after hypophysectomy, performed at 5 or 8 weeks of age, the hypothalamic concentrations of GAL and GAL mRNA were reduced by 30-50% in both male and female rats, compared to age- and sex-matched controls. Similar reverse-phase HPLC retention times of hypothalamic GAL were observed in intact and hypophysectomized rats. The reduction of hypothalamic GAL concentration following hypophysectomy was time-dependent, as peptide levels were unaffected one week after surgery. Immunohistochemistry showed regional differences in the effect of hypophysectomy on galaninergic neurons. In the hypophysiotropic hypothalamus, the scarce GAL immunoreactivity normally observed in the arcuate nuclei was no longer detectable in hypophysectomized rats, and the intense GAL immunoreactivity of the external zone of the median eminence progressively decreased and completely disappeared 3 and 6 weeks after hypophysectomy. In contrast, in the neurohypophyseal system, there was an increase of GAL labelling of the perikarya and emerging axons in the supraoptic and lateral-paraventricular nuclei, 1 and 3 weeks after hypophysectomy, that disappeared 6 weeks after hypophysectomy. An increase of GAL immunoreactivity was also observed in the internal zone of the median eminence 1 week but not 3 weeks after hypophysectomy. We conclude that hypophysectomy reduces the content of GAL and GAL mRNA in the rat hypothalamus. These changes are time-dependent and clearly detected after 3 weeks. The neurohypophyseal and hypophysiotropic galaninergic systems respond differently to hypophysectomy.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Sexual differentiation of growth hormone feedback effects on hypothalamic growth hormone-releasing hormone and somatostatin.
To investigate possible sex differences in the feedback regulation of growth hormone (GH) secretion, concentrations of immunoreactive GH-releasing hormone (GRF) and somatostatin (SS) were measured in the median eminence (ME) and the hypothalamus of male and female rats bearing the MtTW15 tumor, which secretes high amounts of GH and prolactin (PRL). Four weeks after tumor implantation in male rats, the GRF concentration in the whole hypothalamus, including the ME, was decreased by 37% (0.29 +/- 0.02 vs. 0.46 +/- 0.02 ng/mg protein in intact male controls; p less than 0.001) and the concentration of SS was increased by 40% (11.5 +/- 0.7 vs. 8.1 +/- 0.3 ng/mg protein in male controls; p less than 0.01). In female rats, the presence of tumor for 4 weeks caused a smaller (18%) reduction in GRF concentrations (0.27 +/- 0.02 vs. 0.33 +/- 0.03 ng/mg protein in intact female controls; p less than 0.05) and no significant change in SS concentrations (10.2 +/- 0.08 vs. 9.7 +/- 0.8 ng/mg protein in female controls). Tumor-related changes in GRF and SS concentrations were also more pronounced in male rats than in females, when determined separately in the microdissected ME and in the remaining hypothalamus. These differences occurred despite similar increases in serum GH, PRL and insulin-like growth factor I concentrations in male and female tumor-bearing rats. To assess which hormone (GH or PRL) was responsible for these changes, intact male rats were treated for 10 days with 2 daily s.c. injections of rat GH (rGH; 100 and 250 micrograms/day), rat PRL (100 and 250 micrograms/day) or vehicle.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Galanin is a physiological regulator of spontaneous pulsatile secretion of growth hormone in the male rat.
To determine whether galanin (GAL), a 29-amino acid neuropeptide, plays a role in the physiological regulation of the pulsatile secretion of GH and PRL in the male rat, secretory patterns of both hormones were studied in freely moving animals after GAL passive immunoneutralization. Adult male Sprague-Dawley rats were equipped with iv and intracerebroventricular catheters. After 7 days, 3 microliters of a specific GAL antiserum (GAL-AS) or normal rabbit serum (NRS; controls) were infused in the third ventricle of 10 rats, 25 and 1 h before the animals were bled every 15 min for 6 h (1000-1600 h). Plasma GH and PRL concentrations were measured by RIA, and the hormonal secretory patterns were analyzed by the PULSAR program. Control rats, treated with NRS, displayed typical GH secretion, with pulses of high amplitude (167 +/- 27 ng/ml) and low frequency (2.4 +/- 0.2 pulses/6 h), separated by periods of low trough levels (3.8 +/- 0.6 ng/ml). Rats treated with GAL-AS had altered pulsatile GH secretion. Pulse height was markedly reduced (77 +/- 15 ng/ml; P less than 0.01 vs. controls), and peak frequency was higher (3.6 +/- 0.5 pulses/6 h; P less than 0.05), while GH baseline levels and integrated GH secretion over the 6-h sampling period remained unaltered. Injection of rat GH-releasing hormone (1 microgram/rat, iv) caused a similar GH stimulation in both groups of rats, as determined by the peak GH response at 5 min (368 +/- 112 vs. 342 +/- 81 ng/ml) or by the integrated GH response over 1 h (5.13 +/- 1.30 vs. 4.77 +/- 1.15 micrograms.min/ml in NRS- and GAL-AS-treated rats, respectively; P less than 0.05). In contrast to GH, pulsatile secretion of PRL was not affected by the GAL-AS treatment. These results indicate that GAL is a physiological regulator of spontaneous pulsatile secretion of GH, but not PRL, in the male rat. The influence of GAL on GH secretion appears to be exerted within the hypothalamus, mainly by a stimulation of GRF secretion. However, the changes in GH pulse frequency observed after GAL immunoneutralization suggest that GAL might also influence the somatostatin inhibitory tone.
Animals↗
Galaninergic mechanisms are involved in the regulation of corticotropin and thyrotropin secretion in the rat.
Galanin (GAL), a 29-amino acid peptide, affects the secretion of several anterior pituitary hormones, including PRL and GH. Since GAL coexists with vasopressin and CRH in the hypothalamic paraventricular nucleus (PVN), we have studied the pharmacological and physiological actions of GAL on ACTH and TSH secretion in freely moving male rats. Cannulae were surgically implanted in the right atria and brain, intraventricular or adjacent to the PVN, of adult Sprague-Dawley rats. Seven days later, GAL (500 or 1000 ng) or saline was infused into the PVN, and serial blood samples were obtained 5, 10, 20, and 40 min after the infusion. Some animals were also stressed by the inhalation of ether vapors for 2 min after the PVN infusion. Basal ACTH concentrations were increased 2-fold in saline-treated rats; however, plasma ACTH levels were unchanged after GAL infusion. The exposure of rats to ether vapors for 2 min after the infusion of saline into the PVN increased plasma ACTH concentrations from 22.8 +/- 6.0 to 596.6 +/- 59.9 pg/ml 10 min later. However, the infusion of GAL into the PVN attenuated stress-induced ACTH secretion. After GAL infusion, peak ACTH levels (332.7 +/- 84.0 pg/ml) were attained 5 min after ether exposure, followed by a rapid decline at 10 min (P less than 0.001) and 20 min (P less than 0.05). Plasma TSH concentrations were unchanged by GAL or saline infusion and were not affected by ether vapor inhalation. To determine the physiological significance of GAL in the control of ACTH and TSH secretion, endogenous GAL was immunoneutralized by the infusion of 3 microliters GAL antiserum (GAL-AS) into the third cerebral ventricle 25 and 1 h before withdrawing blood samples every 15 min for 6 h. Animals treated with normal rabbit serum (NRS) served as controls. Plasma ACTH concentrations were unchanged by NRS during the 6-h period. However, infusion of GAL-AS raised plasma ACTH concentrations to over 400 pg/ml 75 min after infusion in some animals. In general, plasma ACTH concentrations were increased 4 h of the 6-h sampling period compared to levels in NRS-treated controls. In contrast, GAL-AS reduced TSH concentrations by 50% compared to control values. In contrast to these marked actions of centrally administered GAL, ACTH secretion from dispersed anterior pituitary cells in vitro was unaffected by GAL in concentrations up to 10(-6) M. Furthermore, GAL did not alter CRH (1 nM)-induced ACTH secretion.(ABSTRACT TRUNCATED AT 400 WORDS)
Adrenocorticotropic Hormone↗
Sexual and developmental differences in peptides regulating growth hormone secretion in the rat.
Sex differences in the hypothalamic control of growth hormone (GH) secretion were investigated by measuring rat GH-releasing factor (rGRF) and somatostatin in male and female rats. Rat GRF-like immunoreactivity (rGRF-IR) was higher in the median eminence and hypothalamic tissue outside of the median eminence of adult (90-day-old) male compared to female rats. A similar pattern of rGRF-IR content was found in the median eminence of 35-day-old rats. This sex difference developed between days 25 and 35 of age, during which time serum concentrations of insulin-like growth factor (IGF-1) and body weight increased in both sexes. To a lesser extent, the content of somatostatin-like immunoreactivity (SLI) was higher in the median eminence of adult female rats compared to male rats. Whole hypothalamic rGRF-IR and SLI contents were influenced only moderately by adult gonadectomy or gonadal steroid treatments. For example, estrogen increased rGRF-IR content in castrated rats, but orchidectomy alone or orchidectomy followed by testosterone did not influence rGRF-IR content. Additionally, whole hypothalamic SLI content was unaffected by orchidectomy or orchidectomy followed by testosterone or estrogen. One month after ovariectomy, rGRF-IR and SLI in whole hypothalamic fragments were similar to their respective contents in gonad-intact males. However, ovariectomy followed by estrogen or testosterone did not restore rGRF-IR content and partially restored SLI content to levels seen in gonad-intact females.
Aging↗
Serum lactate dehydrogenase activity increases in both endogenous and exogenous hypercorticisms.
Both endogenous and exogenous hypercorticisms are associated with a modest increase of the activity of serum lactate dehydrogenase. Considering both the wide use of this parameter and the frequent prescription of corticosteroids in clinical practice, awareness of this phenomenon is useful to avoid unnecessary investigations.
Adolescent↗
[Neuroendocrine regulation of eating behavior].
We review current neuroendocrine concepts about feeding behavior. Digestive or metabolic inputs are conveyed to the hypothalamus by endocrine and neuroendocrine pathways (insulin, cholecystokinin). The hypothalamus regulates feeding behavior both quantitatively and qualitatively through several neuroendocrine mediators (neuropeptide Y, galanin, GHRH...). The hypothalamus also integrates, by its communicative network, inputs from the cortex, the sub-cortex, the peripheral metabolism and it modifies consequently the feeding behavior. These neuroendocrine models are developed from many experimental observations both in normal and obese animals.
Animals↗