bluuebunny/crossref_metadata_2025 huggingface dataset:
A null cell adenoma of the pituitary detected seven years after removal of a prolactinoma. Recurrence or de novo tumourigenesis?
Authors: Watanobe Hajime , Kudo Kenji , Okushima Toshimi , Fukita Yohshoh , Takebe Kazuo
Published: June 2009

We report an extremely unusual case of prolactinoma which emerged at recurrence as a null cell adenoma. A 53-year-old woman sought medical attention for progressive visual loss and headache. A pituitary tumour was detected by a computed tomographic scan, and hyperprolactinemia was noted. The tumour, removed by a transfrontal surgery, was a chromophobe adenoma, and immunohistochemically the adenoma cells were selectively positive for PRL, which indicated a prolactinoma. Postoperatively, her plasma PRL level was normalized. Seven years later, she noted blurred vision and again sought medical attention. A CT scan demonstrated recurrence of a pituitary tumour. On this occasion, however, she was not hyperprolactinemic. She underwent again a transfrontal resection of the pituitary tumour. Its histology was again a chromophobe adenoma, but the adenoma cells showed no positive immunostaining for any anterior pituitary hormone including PRL, which indicated a null cell adenoma. We have no clear explanation of the pathogenesis underlying her very unusual course. However, null cells (assuming that the original tumour was a mixed adenoma) left behind at the first surgery, or unidentified hypothalamic and/or pituitary derangements might possibly have been responsible for the recurrence. We learned from this patient that recurrent pituitary adenomas may not necessarily have the same endocrine features as did the original tumours. This information appears to make a valid clinical point, because if hormone levels alone are followed after pituitary surgery, recurrent pituitary tumours may be overlooked.
Clinical heterogeneity of 21-hydroxylase deficiency of sibs with identical 21-hydroxylase genes
Authors: Bormann Michael , Kochhan Lothar , Knorr Dieter , Bidlingmaier Frank , Olek Klaus
Published: June 2009

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is a disorder with different clinical manifestations, that results from mutations in the P-450(c21) gene. Direct sequence analysis of P-4 50(c21) genes in a family demonstrates that patients with different clinical forms of congenital adrenal hyperplasia can have identical P-4 50(c21) genes, suggesting that other effects play a role in developing the different clinical forms.
Glucocorticoid receptor and inhibition of 3-O-methyl-D-glucose uptake by glucocorticoids in peripheral blood leukocytes from normal humans: correlation between receptor level and hormone effect in vitro
Authors: Tanaka Hirotoshi , Akama Hideto , Ichikawa Yoichi , Homma Mitsuo , Makino Isao
Published: June 2009

We have measured the glucocorticoid receptor concentration in mononuclear and polymorphonuclear leukocytes, both of which were isolated from peripheral blood from ten healthy male volunteers. In parallel, the inhibitory effect of dexamethasone on 3-O-methyl-D-glucose uptake was assayed in the corresponding mononuclear leukocytes. The glucocorticoid receptor levels in mononuclear leukocytes correlated with those in polymorphonuclear leukocytes, and there was a linear relationship between the cellular glucocorticoid receptor levels and glucocorticoid-mediated inhibition of the uptake of 3-O-methyl-D-glucose in mononuclear leukocytes. When mononuclear leukocytes were incubated in the presence of 8-bromo-cAMP, cellular glucocorticoid receptor levels increased and a more pronounced inhibitory effect of dexamethasone was observed on the transport of 3-O-methyl-D-glucose. We conclude that the cellular glucocorticoid receptor levels in peripheral blood leukocytes reflect in vitro responsiveness to glucocorticoids in mononuclear leukocytes from healthy males, and that the individual responsiveness may alter upon changes in the cellular levels of glucocorticoid receptor.
Importance of atrial natriuretic hormone in an exaggerated natriuresis during acute sodium load in primary aldosteronism
Authors: Kawabe Hiroshi , Furukawa Tomohiro , Saito Ikuo , Saruta Takao
Published: June 2009

To elucidate the factors which contribute to the exaggerated natriuresis in primary aldosteronism, hemodynamic and hormonal changes induced by saline infusion (at a rate of 0.5 1/h for 3 h) were examined in 6 patients with primary aldosteronism, 13 with essential hypertension, and 8 normotensive subjects. After saline infusion, increases in urinary sodium excretion, glomerular filtration rate, atrial natriuretic hormone, and urinary dopamine excretion along with suppression of plasma renin activity and aldosterone were compared in the three groups. All three groups demonstrated similar increases in glomerular filtration rate, but patients with primary aldosteronism did not show changes in urinary dopamine excretion, plasma renin activity, and aldosterone, despite their increased excretion of sodium. The increase in plasma atrial natriuretic hormone was significantly greater in primary aldosteronism than in essential hypertension or normotensive subjects. No changes in blood pressure or heart rate were seen. These findings suggest that atrial natriuretic hormone might play a role in the exaggerated excretion of sodium in patients with primary aldosteronism.
Ontogenic differences in the nutritional regulation of circulating IGF binding proteins in sheep plasma
Authors: Gallaher Brian W , Breier Bernhard H , Oliver Mark H , Harding Jane E , Gluckman Peter D
Published: June 2009

Well-fed castrated male sheep (N= 3) and 125 days gestation pregnant ewes (N = 6) with chronically catheterized fetuses were fasted for 72 h. Insulin-like growth factor-binding protein (IGFBP) levels in fed and starved fetal, maternal and castrated male sheep plasma were measured using ligand blot analysis. IGFBPs in adult and fetal sheep differed in distribution both before and after 72 h starvation. IGFBP-3 was the major postnatal binding protein, while in the fetus IGFBP-2, IGFBP-3 and the circulating IGF type 2 receptor fragment each contributed 2 5–30% of total IGF binding capacity. After starvation, total IGF binding capacity and IGFBP-3 fell in plasma of maternal and castrated male sheep (p<0.05). Total IGF binding capacity rose with starvation in fetal plasma (p <0.05) as a result of an increase in IGFBP-1 (p< 0.01) and IGFBP-2 (p<0.05). The different nutritional control of the IGFBPs in the fetus and the adult may reflect ontogenic differences in the regulation and function of circulating IGFs and their binding proteins.
Thyrotropin action is impaired in the thyroid gland of old rats
Authors: Reymond Frédéric , Dénéréaz Nicole , Lemarchand-Béraud Thérèse
Published: June 2009

Aging in rats is characterized by low plasma concentrations of thyroid hormones with unchanged levels of TSH, suggesting an altered TSH action in addition to the impaired regulation of TSH secretion. To evaluate TSH action we determined TSH binding to thyroid membranes of young and old male rats (3–4 and 24–26 months of age), as well as the activity of adenylate cyclase in basal and stimulated conditions. Saturation analyses of [125I]-bTSH to thyroid membranes in the presence of increasing quantities of unlabelled bTSH (0.03–100 mU) show two types of binding sites, one of high affinity (Ka 1.5 109 mol l−1) the other of lower affinity (Ka 1.2 108 mol l−1), which are similar in both age groups. The number of TSH binding sites of high affinity is less in old rats than in young rats (7.6±0.9 vs 14.8±1.1 TSH mU/mg protein, N = 11 and 10 respectively, p< <0.001), whereas the number of binding sites of low affinity is not significantly different (76.0±8.2 vs 99.1±9.0 TSH mU/mg protein). The activity of adenylate cyclase determined in basal conditions is similar in both old and young rats (1.11±0.12 vs 1.04±0.9 nmol cAMP/2 h x mg/protein). TSH (10 mU) induced a significant increase in cAMP formation with the thyroid membranes from young rats but not with those from old rats. In contrast, the stimulation of cAMP formation by GTP (2 mmol/l) or forskolin (10 mmol/l), two direct stimulators of adenylate cyclase, is similar in both groups of rats (200% and 250%, respectively). These data suggest that the reduced action of TSH on the thyroid gland of old rats is due to the decreased number of TSH binding sites, which may also be partly responsible for the low thyroid hormone secretion with aging in spite of the unchanged levels of TSH. A postreceptor defect does not seem to be involved, since direct stimulations of adenylate cyclase by GTP or forskolin are just as effective in old rats as in young rats.
Functional expression of human myometrial endothelin receptors in Xenopus laevis oocytes
Authors: Kimura Tadashi , Azuma Chihiro , Saji Fumitaka , Tokugawa Yoshihiro , Takemura Masahiko , Miki Mariko , Ono Masaaki , Mori Kensaku , Tanizawa Osamu
Published: June 2009

We demonstrate the existence of functional endothelin receptors in human uterine myometrium using the Xenopus oocyte expression system. Fifty nanograms of poly(A) +RNA from myometrium was injected into Xenopus laevis oocytes and incubated for 70–80 h. The membrane potential of the oocyte was clamped at −60 mV and membrane current was measured during and after endothelin stimulation. Endothelin-1 elicited a large inward membrane current in the oocytes injected with poly(A) +RNA; endothelin-2 elicited a small current; while endothelin-3 did not induce any membrane current. These results indicate the existence of messenger RNA encoding functional endothelin-1 receptors in human uterine myometrium.
Polarized efflux of iodide in porcine thyrocytes occurs via a cAMP-regulated iodide channel in the apical plasma membrane
Authors: Nilsson Mikael , Björkman Ulla , Ekholm Ragnar , Ericson Lars E
Published: June 2009

The intracellular regulation of thyrotropin-stimulated iodide efflux was studied in polarized porcine thyrocytes grown as a continuous, tight monolayer in bicameral culture chambers. From a previous study using this system we know that thyrotropin rapidly increases iodide efflux in the apical but not basal direction of the polarized epithelium. [125I]-iodide efflux in apical direction was stimulated by thyrotropin in a concentration-dependent manner (1–10 U/I), whereas efflux in basal direction was unchanged at any thyrotropin dose. Thyrotropin-induced elevation of intracellular cAMP showed a corresponding concentration dependence. The selective stimulation of apical efflux by thyrotropin was evident also when re-uptake of iodide released in basal direction was blocked by perchlorate. The effect of thyrotropin on apical efflux was mimicked by 8-bromo-cAMP and forskolin, whereas agents known to activate the Ca2+/phosphatidylinositol cascade (epidermal growth factor) and protein kinase C (phorbol ester) or increase cytosolic [Ca2+] (A23187) were inactive. We conclude that the selective stimulation by thyrotropin of apical iodide efflux, corresponding to efflux in luminal direction in intact follicles, occurs via cAMP-regulated iodide channels present in the apical domain of the plasma membrane.
Progressive and concurrent deterioration of vagus-stimulated and hypoglycemia-induced glucagon secretion in streptozotocin-diabetic rats
Authors: Hertelendy Zsolt I , Patel DG , Skau Kenneth A
Published: June 2009

The effects of left cervical vagus nerve stimulation on glucagon secretion were studied in streptozotocin-diabetic and age-matched control adult male rats. At two-week intervals, after the induction of streptozotocin-diabetes, streptozotocin-diabetic and age-matched control rats were anesthetized with chloral hydrate (350 mg/kg, ip). Left cervical vagus nerves were electrically stimulated via a Grass stimulator with 5-volt monophasic pulses of 3 msec duration at a frequency of 20 Hz for 1, 2, and 4 min. Arginine-induced glucagon secretion was also determined. Vagus nerve-stimulated (2 and 4 min) glucagon secretion deteriorated as the duration of streptozotocin-diabetes increased. Glucagon secretion in response to vagus nerve stimulation was virtually absent by 12 weeks of streptozotocin-diabetes. However, arginine-induced glucagon secretion was unaffected. Subsequent experiments showed that the defect in glucagon secretion from vagal stimulation occurred concurrently with that seen from insulin-induced hypoglycemia. These results indicate that the impaired hypoglycemia-induced glucagon secretion in long-term streptozotocin-diabetic rats may be correlated with the deterioration of the parasympathetic nervous system transmission in streptozotocin-diabetes.
Reproducibility of 24-h growth hormone profiles in children
Authors: Albertsson-Wikland Kerstin , Rosberg Sten
Published: June 2009

The rate of GH secretion and the pattern of GH peaks were compared in a group of nine prepubertal children during their prepubertal period in repeated 24-h GH profiles. At investigation, the children were 6–1 3 years old (at first profile 6–11 years old) and of normal height (±2 sd). Two profiles were obtained per child, (with a mean time interval of 1.5 years, range 0.7 to 3.5 years. The calculated GH secretions of the first and second profiles were compared. As a group, no significant differences in secreted amount of GH, when expressed as data from the second profile as a percentage of data from the first profile (93±8%), number of peaks (98±7%) or mean peak amplitudes (92±11%), were obtained. Between the repeated curves of an individual child, maximal difference in secretion, number of peaks and mean peak amplitudes ranged around±30%, with a mean intraindividual cv of 12%. The reproducibility in the peak distribution for all profiles was also analysed. The relative frequencies is a percentage of the GH peak amplitudes and peak widths were virtually identical in the repeated profiles. Reproducibility of the temporal pattern of profiles was analysed using time-series analysis (Fourier analysis) and showed no difference in rhythmicity between the different occasions. In conclusion, a high reproducibility of both GH secretion and GH pattern was found for the whole group of prepubertal children. The high degree of reproducibility of the 24-h GH profiles of the whole group of children indicated that the information from these curves, in terms of both pattern and total secretion, can be used for clinical as well as for physiological purposes. The intraindividual reproducibility was less pronounced, however, leading to a sound scepticism when relating biological phenomena to a single profile of an individual child.
Activation of cholinergic tone by pyridostigmine reverses the inhibitory effect of corticotropin-releasing hormone on the growth hormone-releasing hormone-induced growth hormone secretion
Authors: Corsello SM , Tofani A , Casa S Della , Sciuto R , Rota CA , Colasanti S , Bini A , Barini A , Barbarino A
Published: June 2009

Previous studies have shown that corticotropin-releasing hormone (CRH) is capable of inhibiting growth hormone (GH) secretion in response to GH-releasing hormone (GHRH). In an attempt to clarify the mechanism of the CRH action, we have studied the effect of enhanced cholinergic tone induced by pyridostigmine on the CRH inhibition of the GH response to GHRH in a group of six normal men and six normal women. All subjects presented a normal GH response to 50 μg iv GHRH administration (mean peak±sem plasma GH levels 20±2.9 μg/l in men and 28.9±2.9 μg/l in women) with a further significant increase after pyridostigmine pretreatment (60mg orally given 60 min before GHRH) in men (GH peaks 43.1±6.9 μg/l, p<0.005) but not in women (GH peaks 39.2±3.0 μg/l). In the same subjects, peripherally injected CRH (100 μg) significantly inhibited the GH response to GHRH (GH peaks 8.1±0.6 μg/l in men, p<0.005 and 9.9±0.7 μg/l in women, p<0.005). Pyridostigmine (60 mg) given orally at the same time of CRH administration (60 min before GHRH) reversed the CRH inhibition of GHRH-induced GH secretion (GH peaks 35.3±8.2 μg/l in men and 35±3.3 μg/l in women) with a response not significantly different to that seen in the pyridostigmine plus GHRH test. Our data confirm that pyridostigmine is capable of potentiating the GHRH-induced GH release in normal male but not female subjects. In addition, our studies show that the potentiating action of pyridostigmine on the GHRH-induced GH secretion prevails on the inhibiting effect of CRH when the two drugs are given together 1 h before GHRH injection. Both CRH and pyridostigmine could exert their action by modifying, in opposite ways, somatostatin release from the hypothalamus.
The effect of atenolol on the growth hormone response to growth hormone-releasing hormone in obese children
Authors: Loche Sandro , Pintus Stefano , Carta Daniela , Muntoni Anna Carla , Congiu Gabriella , Civolani Patrizia , Pintor Carlo
Published: June 2009

We have evaluated the effect of acute administration of atenolol, a selective β-adrenergic antagonist, on the GH response to GHRH in nine obese children and in eight age-matched controls. The GH response to GHRH (1–29, 1 μg/kg iv), evaluated both as the GH peak and as integrated area under the curve, was significantly lower in the obese children than in the controls. Pretreatment with atenolol (50 or 100mg orally in subjects with body weight 40 kg, respectively, administered 120 min before the GHRH injection) significantly increased the GH response to GHRH in the obese subjects, such that their mean peak GH levels and mean integrated area under the curve after atenolol plus GHRH were similar to those of the control children after GHRH. Also in control children, atenolol caused a significant augmentation of the GH response to GHRH. Mean peak GH levels and mean integrated area under the curve after atenolol plus GHRH were significantly higher in the controls than in the obese children given the same treatment. These data show that inhibition of central β-adrenergic receptors counteracts the blunted GH response to GHRH present in the obese children. In view of the alleged mechanism of action of β-adrenergic blockade (inhibition of endogenous SRIH release), our data suggest that the somatostatinergic system is intact in obesity, and that the suppressed GH secretion is due to other causes.
Thyroid hypoechogenic pattern at ultrasonography as a tool for predicting recurrence of hyperthyroidism after medical treatment in patients with Graves' disease
Authors: Vitti Paolo , Rago Teresa , Mancusi Francesco , Pallini Stefania , Tonacchera Massimo , Santini Ferruccio , Chiovato Luca , Marcocci Claudio , Pinchera Aldo
Published: June 2009

An abnormal thyroid echographic pattern characterized by a diffuse low echogenicity has been described in Hashimoto's thyroiditis and Graves' disease. The aim of the present work was to study the relationship between thyroid hypoechogenicity and the outcome of treatment for hyperthyroidism with antithyroid drugs in patients with Graves' disease. The study group included 105 patients who underwent a course of methimazole treatment. Thyroid ultrasonography was carried out at diagnosis, and autoantibodies to thyrotropin receptor (TR-ab) were measured at the end of treatment. During the follow-up after methimazole treatment, 87/105 (83%) patients had relapse of hyperthyroidism and 18/105 (17%) were in remission. Recurrence of hyperthyroidism occurred in 71/76 (93%) patients with thyroid hypoechogenicity and in 16/29 (55%) of those with normal thyroid echogenicity (ϰ2= 19.0; p<0.0001). Positive TR-ab values at the end of methimazole treatment were found in 59/76 (78%) patients with thyroid hypoechogenicity and in 12/29 (41%) patients with normal thyroid echogenicity (ϰ2 = 10.9; p< 0.0001). Sixty-five/87 (74%) patients with relapse of hyperthyroidism and 6/18(3 3%) of those who remained euthyroid were TR-ab-positive at the end of methimazole treatment (ϰ2 = 9.8; p< 0.002). The finding of thyroid hypoechogenicity at diagnosis had higher specificity (0.81) and sensitivity (0.72) with respect to TR-ab positivity at the end of methimazole treatment (0.74 and 0.66 respectively) for the prediction of relapse of hyperthyroidism. Therefore, the evaluation of thyroid echographic pattern can be considered a useful prognostic tool in patients with Graves' disease.
Cyclophosphamide-induced disturbance of gonadotropin secretion manifesting testicular damage
Authors: Hoorweg-Nijman Jantine JG , de Waal Henriette A Delemarre-van , de Waal Frans C , Behrendt Henk
Published: June 2009

Gonadal function was evaluated in 23 men (aged 14.8–28.8 years) treated in childhood with cytotoxic drugs for a solid tumour. Group 1 (N = 14) had been treated with non-alkylating drugs only, while group 2 (N=9) received the alkylating drug cyclophosphamide in addition (range 3.8–19.5 g/m2). Median age at the start of treatment was 4.6 years (range 0.6–16.1) in group 1 and 13.9 years (range 3.7–16.9) in group 2. Data of the patients were compared with a reference group consisting of 14 normal men. Almost all patients of both groups showed normal development of puberty; 13 of the 14 men in group 1 showed normal hormonal values. In group 2, basal LH and FSH as well as the LH and FSH responses to GnRH showed higher levels compared to those of a reference group (p<0.001). Correlation analysis showed an evident correlation between the total dose of received cyclophosphamide and the basal FSH level (r=0.78; p=0.002), the FSH response to GnRH (r=0.73; p=0.002) and the LH response to GnRH (r=0.67; p=0.002). There was no correlation between the hormonal parameters and the doses of the other cytotoxic drugs. Semen analysis showed azoospermia in four boys of group 2 and in none of group 1. Two patients in group 2 had an elevated FSH response to GnRH while their semen analysis was normal. Conclusions: (1) There is a dose-response relationship between the basal FSH. the LH and FSH responses to GnRH and the dose of cyclophosphamide. In all cyclophosphamide-treated patients the FSH response to GnRH increased. (2) Increased gonadotropin secretion can be found while semen analysis is normal; an increased FSH response to GnRH can be the first manifestation of testicular damage. (3) Evaluation of gonadotropins, both basal and stimulated LH and FSH values, is an easy and useful method for following up gonadal function in cyclophosphamide-treated men, especially for detecting early and subtle testicular damage.
The interrelationship between and the regulation of hepatic growth hormone receptors and circulating GH binding protein in the pig
Authors: Ambler Geoffrey R , Breier Bernhard H , Surus Andrzej , Blair Hugh T , McCutcheon Stuart N , Silbergeld Aviva , Gluckman Peter D
Published: June 2009

We evaluated the interrelationship between, and regulation of, the hepatic growth hormone receptor and serum GH binding protein (GH BP) in pigs treated with recombinant porcine growth hormone (rpGH). Infant and pubertal male pigs (N = 5 per group) received either rpGH 0.15 mg/kg daily or diluent intramuscularly for 12 days. Somatic growth, serum IGF-I and GH BP and [125I]bovine GH (bGH) binding to MgCl2-treated hepatic membrane homogenates were examined. Marked age-related increases were seen in serum GH BP (p<0.001) and [125I]bGH binding to hepatic membranes (p<0.001). GH BP was increased in rpGH treated animals (p = 0.03), from 13.8±1.2 (mean±1 x sem) (controls) to 17.8±2.0% in infants, and from 35.2±2.6 (controls) to 41.8±3.4% in pubertal animals. [125I]bGH binding to hepatic membranes was also increased by rpGH treatment (p<0.05), from 7.0±1.6 (controls) to 15.4±3.6% in infants and from 53.7±7.1 (controls) to 65.1±11.8% in pubertal animals. No significant interaction between age and treatment was seen. Overall, serum GH BP correlated significantly with [125I]bGH membrane capacity (r=0.82, p<0.001), with a correlation of r= 0.83 in the infant animals but no significant correlation in the pubertal animals considered alone (r=0.13). Serum IGF-I correlated significantly with serum GH BP (r=0.93, p<0.001) and [125]bGH membrane binding capacity (r = 0.91, p< 0.001). These observations suggest that serum GH BP levels reflect major changes of hepatic GH receptor status. In addition, the present study demonstrates that the hepatic GH receptor can be induced by GH in the infant pig, despite a developmentally low GH receptor population at this age, suggesting potential efficacy of GH at earlier ages than generally considered.
Impaired induction of prolactin secretion from the anterior pituitary by suckling in streptozotocin-induced diabetic rat
Authors: Ikawa Hiroshi , Irahara Minoru , Matsuzaki Toshiya , Saito Seiichiro , Sano Toshiaki , Aono Toshihiro
Published: June 2009

Prolactin (PRL) secretion in streptozotocin-induced diabetic rats postpartum was examined to elucidate the reason for the reduced milk secretion of diabetic mothers. Pregnant Wistar rats were given citrate buffer (control group) or streptozotocin only (DM group) or with insulin (insulin group). Growth of pups was significantly lower in the DM group than in the control group, but similar in the insulin and control groups. Suckling-induced PRL secretion was significantly lower in the DM group than in the control group, and intermediate in the insulin group. TRH-induced PRL secretion was significantly lower in the DM group than in the control group, but the same in the insulin and control groups. Histologically, the mammary glands in the DM group were relatively less developed than those in the control group. The results suggest that reduced milk secretion in diabetic mothers is due to impaired induction by suckling of PRL secretion from the anterior pituitary as well as poor development of the mammary gland.
The effects of an anabolic steroid (oxandrolone) on reproductive development in the male rat
Authors: Grokett Bernard H , Ahmad Nazir , Warren Dwight W
Published: June 2009

Oxandrolone is a 5α-reduced anabolic steroid that is administered for the treatment of short stature disease in children. It is a commonly used substance beginning as early as prepuberty by some individuals who are seeking to enhance athletic performance or personal appearance. Because of the lack of data on the effects of anabolic steroids on the reproductive system, we have examined the effects of oxandrolone treatment on reproductive development in male rats with treatment beginning two days after weaning. Male, Sprague-Dawley rats (N=12) received a daily subcutaneous injection of oxandrolone (32.7 μmol·kg−1·day−1) and the control group (N= 12) received vehicle only (dimethyl sulfoxide). Treatment began at age 23 days and continued to 60 days of age. The weights of the testes, prostate glands, and seminal vesicles in the treatment group were 69%, 50% and 29% below control levels, respectively and were all significantly decreased (p<0.01). Testicular testosterone production in a 3-h incubation was inhibited in the treated animals to 1.3% of control values (p<0.001). Serum FSH (11.7% of control) and LH (undetectable) in the treated animals were both significantly less than controls. Histological findings indicated an arrest of advanced spermatids and a severe depletion of Leydig cells in the interstitial compartment. It was concluded that treatment of immature male rats with oxandrolone results in effects on the adult male reproductive system which are profound and occur at several levels. The most likely affected sites are the hypothalamus, pituitary gland, and the Leydig cells.
Invasive mixed growth hormone/prolactin secreting pituitary tumour: complete shrinking by octreotide and bromocriptine, and lack of tumour growth relapse 20 months after octreotide withdrawal
Authors: Sadoul Jean-Louis , Thyss Antoine , Freychet Pierre
Published: June 2009

Octreotide and bromocriptine were used to treat an acromegalic patient harbouring an invasive pituitary tumour secreting growth hormone and prolactin. Octreotide (100 μg, subcutaneously, three times daily) and bromocriptine (15 mg orally, daily) rapidly improved clinical signs and symptoms, including diabetes that initially required insulin. Complete control of growth hormone and prolactin secretion was obtained and maintained by this treatment protocol for 12 months without affecting the other pituitary functions. A major tumour shrinkage was apparent by magnetic resonance imaging after six months, and was considered to be complete after 12 months of treatment. Octreotide was then discontinued without any relapse in either growth hormone secretion or tumour growth over a 20-month period following withdrawal. Attempts were made to discontinue bromocriptine, but a maintenance therapy (2.5 mg daily) was required to control rebounds of prolactin hypersecretion. Two months after octreotide withdrawal, acute pancreatitis secondary to cholelithiasis required surgery; this complication was attributed to octreotide (pre-treatment ultrasonography was normal). These findings suggest that combination therapy with octreotide and bromocriptine may be considered in pituitary macroadenomas secreting growth hormone and prolactin. They also emphasize the need for a close monitoring of cholelithiasis, not only during octreotide therapy but also after the drug's withdrawal.
Temporal coupling among luteinizing hormone, follicle stimulating hormone, β-endorphin and cortisol pulse episodes in vivo
Authors: Veldhuis Johannes D , Johnson Michael L , Seneta Eugene , Iranmanesh Ali
Published: June 2009

We have applied explicit probability equations to assess possible non-random associations among four distinct hormone series consisting of episodic luteinizing hormone, follicle stimulating hormone, β-endorphin, and/or cortisol pulses observed under physiological conditions in normal men. Closed-form likelihood functions permitted us to demonstrate significantly coordinated patterns of multiple hormone release. A specific quadruple co-pulsatility pattern was observed, in which the two gonadotropic hormones (luteinizing hormone and follicle stimulating hormone) were co-secreted and coupled by a 10-20 min lag to the later release of β-endorphin. In turn, β-endorphin release episodes were followed within 0–30 min by cortisol bursts. Conditional probability analysis allowed us to reject with high statistical confidence the null hypothesis that this unique temporally specified pattern of quadruple hormone release was due to purely random associations among the four pulsatile series. We conclude that discrete hormone release episodes associated with four hormones within the gonadotropic and corticotropic axes in man exhibit significantly lagged non-random temporal coupling in vivo.
Effects of a two-hour early awakening and of bright light exposure on plasma patterns of cortisol, melatonin, prolactin and testosterone in man
Authors: Touitou Y , Benoit O , Foret J , Aguirre A , Bogdan A , Clodoré M , Touitou C
Published: June 2009

Bright light is a synchronizing agent that entrains human circadian rhythms and modifies various endocrine and neuroendocrine functions. The aim of the present study was to determine whether and how the exposure to a bright light stimulus during the 2 h following a 2 h earlier awakening could modify the disturbance induced by the the sleep deprivation on the plasma pattens of hormones whose secretion is sensitive to light and/or sleep, namely melatonin, prolactin, cortisol and testosterone. Six healthy and synchronized (lights on: 07.00–23.00) male students (22.5±1.1 years) with normal psychological profiles volunteered for the study in winter. The protocol consisted of a baseline control night (customary sleep schedule) followed by three shortened nights with a rising at 05.00 and a 2 h exposure to either dim light (50 lux; one week) or bright light (2000 lux: other week). Our study showed a phase advance of the circadian rhythm of plasma cortisol without significant modifications of the hormone mean or peak concentration. Plasma melatonin concentration decreased following bright light exposure, whereas no obvious modifications of plasma testosterone or prolactin patterns could be observed in this protocol.
The nocturnal thyroid-stimulating hormone surge is absent in overt, present in mild primary and equivocal in central hypothyroidism
Authors: Adriaanse Ria , Romijn Johannes A , Endert Erik , Wiersinga Wilmar M
Published: June 2009

The nocturnal TSH surge was studied in controls, in 34 patients with hypothalamic/pituitary disease and in 21 patients with primary hypothyroidism. It was absent in 5/12 hypothyroid patients and in 5/22 euthyroid patients with hypothalamic/pituitary disease (42% vs 23%. NS). Central hypothyroidism relative to euthyroidism was associated with a lower absolute (0.3±0.4 vs 0.9±1.0 mU/l, p<0.05) and relative (24±31 vs 63±51%, p<0.05) nocturnal rise in TSH. In primary hypothyroidism, the nocturnal TSH surge was absent in eight often patients with overt, in one of five patients with mild and in none of six patients with subclinical hypothyroidism. The relative nocturnal rise in TSH was normal in mild (54±33%) and subclinical (92±69%), but decreased in overt hypothyroidism (2±10%). Plasma T4 was positively and 09.00 plasma TSH negatively related to the relative nocturnal TSH surge in primary hypothyroidism, but not in central lesions. In both conditions, however, a positive relationship was observed between the relative nocturnal TSH surge and the relative increase of TSH to TRH. In conclusion: (a) The nocturnal TSH surge is usually absent in overt hypothyroidism but present in mild primary hypothyroidism and equivocal in central hypothyroidism. This limits its usefulness as an adjunct in the diagnosis of central hypothyroidism. (b) The magnitude of the nocturnal TSH surge in patients with hypothalamic/pituitary disease or primary hypothyroidism is directly related to the TSH response to TRH, and thus appears to be determined by the directly releasable TSH pool of the pituitary.
Plasma vasopressin and atrial natriuretic hormone levels in hypopituitarism with and without hydrocortisone treatments: responses to an acute water load
Authors: Kimura Tokihisa , Ota Kozo , Shoji Masaru , Inoue Minoru , Sato Kazutoshi , Ohta Masahiro , Yamamoto Tadasu , Shimizu Yasuyuki , Yoshinaga Kaoru
Published: June 2009

To assess whether arginine vasopressin and atrial natriuretic hormone participate in impaired urinary dilution and excretion in glucocorticoid deficiency secondary to hypopituitarism. an acute oral water load of 20 ml·kg−1 BW was undertaken in the absence and presence of an oral hydrocortisone (60 mg) treatment in patients with ACTH deficiency (N= 7) and panhypopituitarism (N = 2). Plasma arginine vasopressin and atrial natriuretic hormone and renal water handling were simultaneously determined and compared with those in similarly water-loaded normal subjects. Plasma arginine vasopressin did not fall in response to decreased blood osmolality after an acute water load in the absence of hydrocortisone; plasma atrial natriuretic hormone did not change despite blood volume expansion; and impairment in urinary dilution and excretion remained. On the other hand, in the presence of hydrocortisone, plasma arginine vasopressin fell in response to a decrease in plasma osmolality and plasma atrial natriuretic hormone increased, thereby restoring urinary dilution and excretion. These results demonstrate that the impaired arginine vasopressin response to acute water loading play an essential role in deranged renal water and electrolyte handling in the state of glucocorticoid deficiency; the impaired release of atrial natriuretic hormone also may affect these disorders.
Longitudinal study of bone loss after thyroidectomy and suppressive thyroxine therapy in premenopausal women
Authors: Pioli Giulio , Pedrazzoni Mario , Palummeri Ernesto , Sianesi Mario , Del Frate Roberto , Vescovi Pier Paolo , Prisco Maria , Ulietti Vittorio , Costi Daniele , Passeri Mario
Published: June 2009

The effects of suppressive doses of L-thyroxine on the appendicular and axial bone mineral content were followed for 12–36 months after total or subtotal thyroidectomy in 15 premenopausal women. Compared to age-matched controls, these patients had a more marked bone loss of the spinal bone mineral content (2.6±1.9% vs 0.2±1.2% per year). The changes in radial cortical bone density were not significantly different from the control group. We conclude that when a suppressive therapy with L-thyroxine is necessary the rate of bone loss should be monitored at regular intervals.
Bromocriptine treatment over 12 years in acromegaly: effect on growth hormone and prolactin secretion
Authors: Rau Harald , Althoff Peter-Henning , Schmidt Kurt , Usadel Klaus Henning
Published: June 2009

It is not known whether bromocriptine treatment in acromegaly can be implemented for a life-long period. To elucidate this problem, the secretory GH and PRL states of 12 patients with acromegaly were determined, before bromocriptine treatment, under therapy (15.0±6.8 mg/day for 12±3 years; mean±sd) and during two-weeks long drug withdrawal after long-term treatment, respectively. Before therapy, all patients showed'a non-sufficient GH suppression after oral glucose load (>2 μg/l), whereas under dopaminergic treatment the post-glucose GH levels of three patients fell below 2 μg/l; normal IGF-I concentrations were found in five patients. However, under bromocriptine, only two patients showed GH suppressions below 2 μg/l following glucose, accompanied with normal IGF-I levels. During bromocriptine withdrawal, GH secretion at 60 min in the oral glucose tolerance test increased significantly (17.0±15.5 vs 5.7±5.2 μg/l; p<0.01); the mean IGF-I level rose from 2.1±0.8 to 4.9±2.2 kU/l (p <0.01). IGF-I was normal during bromocriptine cessation in only one patient; none of the 12 patients showed a GH suppression below 2 μg/l after oral glucose load. Under dopaminergic treatment hyperprolactinemia could not be detected. In conclusion, bromocriptine led to a stable suppression of both GH hypersecretion and—if present—concomitantly elevated PRL levels. Severe side effects or a further tumor growth could not be observed. Thus, the data of the longest follow-up investigation that has so far been published indicate that effective life-long bromocriptine therapy seems to be possible in selected patients with acromegaly.
Hypocalcemia and parathyroid hormone responsiveness in diabetes mellitus: a tri-sodium-citrate clamp study
Authors: Schwarz Peter , Sørensen Henrik A , Momsen Günther , Friis Thorkild , Transbøl lb , McNair Peter
Published: June 2009

The aim of this study was to elucidate the diabetic hypocalcemia and PTH responsiveness, investigated by measuring blood ionized calcium and serum intact parathyroid hormone (S-PTH(1–84)) concentrations, before and during an induced and maintained controlled hypocalcemia. In 15 patients with insulin-dependent diabetes mellitus and 19 healthy volunteers the blood ionized calcium concentration was lowered by about 0.20 mmol/l and maintained at this level by blood ionized calcium controlled tri-sodium-citrate infusion. In patients vs controls, baseline measurements averaged for blood ionized calcium (mmol/l) 1.18±0.08 vs 1.24±0.03 (p<0.01), for S-magnesium (mmol/l) 0.73±0.07 vs 0.81±0.07 (p<0.01) and for S-PTH (1–84) (pmol/l) 3.0±1.0 vs 3.1±1.0 (p>0.75). During the clamp. S-PTH (1–84) peaked to comparable maximums after 5–10 min in both groups and then declined to constant concentrations two to three times above their control levels. In conclusion, we found a diabetic hypocalcemia and hypomagnesemia, though baseline levels of PTH and PTH responsiveness were normal. This may be taken to indicate a mild shift downwards in the set-point for PTH secretion in patients with insulin-dependent diabetes mellitus.
The effect of selective β1-blockade on glucose thresholds for release of counterregulatory hormones and symptoms in insulin-dependent diabetes mellitus
Authors: Vea Hanne , Jorde Rolf , Sager Georg , Vaaler Stein , Sundsfjord Johan
Published: June 2009

To evaluate the effect of β1-blockade (metoprolol) on the plasma glucose thresholds initiating counterregulatory hormone responses and symptoms of hypoglycemia, we used a modified glucose clamp technique to produce a standardized gradual glucose decline from 5.0 to 2.0 mmol/l in nine patients with insulin-dependent diabetes mellitus (IDDM) (HbAlc range 6.7–10.3%, duration of diabetes 5–18 years, autonomous neuropathy present in three of the patients). The responses were studied once with metroprolol and once with placebo, in random order. With the β1-selective blockade, epinephrine release was triggered at a significantly higher (p<0.02) plasma glucose level (3.5 mmol/l) than it was with placebo (3.0 mmol/l). Metoprolol did not change thresholds for growth hormone (3.7/3.5 mmol/l), cortisol (2.9/2.9 mmol/l), glucagon (2.8/2.8 mmol/l) or for pancreatic polypeptide (2.8/2.7 mmol/l). The peak responses of epinephrine and growth hormone were significantly higher (p<0.01) with the β1-blockade. Metoprolol did not change the thresholds for neuroglycopenic and autonomic symptoms. Six out of the seven patients who answered yes to having hypoglycemia did so at a higher blood glucose with metoprolol than without. In our study, the β1-selective blockade altered the responses of counterregulatory hormones, but it did not change the thresholds for hypoglycemic symptoms.
Is thyrotropin-releasing hormone immunoreactivity in peripheral blood an estimate for hypothalamic thyrotropin-releasing hormone release?
Authors: de Greef Wim J , Rondeel Jan MM , Heide Rogier , Klootwijk Wim , Visser Theo J
Published: June 2009

The significance of TRH for pituitary function is still unresolved mainly due to limitations in determining in vivo hypothalamic TRH release. We therefore examined whether TRH immunoreactivity (TRH-IR) in peripheral blood is an index for hypothalamic TRH release. Peripheral TRH-IR varied between 10 and 55 pmol/l and was similar in euthyroid and hypothyroid rats, but lower in hyperthyroid rats. Destruction of the hypothalamic paraventricular area reduced peripheral TRH-IR, while stimulation of this area increased it. Clearance of TRH during continuous TRH infusion was 1.9±0.2, 3.5±0.3 and 5.9±0.8 ml/min in hypothyroid, euthyroid and hyperthyroid rats, respectively. These and previous data on TRH in hypophysial portal blood indicate that 5–25 pmol TRH/I peripheral blood is of hypothalamic origin. Chromatography revealed that TRH-IR from hypothalamus and portal blood co-eluted with TRH, but in peripheral blood two peaks were found, one of which was authentic TRH. Thus, peripheral TRH-IR alters in experimental conditions and part of it seems to be of hypothalamic origin. However, the presence of TRH-like material in peripheral blood not identical to TRH and the fact that experimental conditions alter TRH clearance indicate that peripheral TRH-IR is not an index for hypothalamic TRH release.
Maturation and insulin-like immunoreactivity in rat submandibular salivary glands: possible implication of G regulatory proteins
Authors: de Périère D Deville , Puech R , Hillaire-Buys D , Ribes G
Published: June 2009

Streptozotocin-induced diabetes is accompanied by an increase in insulin-like immunoreactivity concentration in rat submandibular salivary glands. In this study we have examined whether, in normal state, maturation is accompanied by changes in insulin-like immunoreactivity concentration of rat submandibular salivary glands. Insulin-like immunoreactivity concentrations of submandibular salivary glands were significantly higher in 11 months old rats compared with 3.5 months old control animals. A pertussis toxin pretreatment provoked an increase in insulin-like immunoreactivity, suggesting that a pertussis toxin sensitive G-protein is involved in the regulation of insulin-like immunoreactivity in the rat submandibular salivary glands.
The pars tuberalis of the hypophysis: a modulator of the pars distalis?
Authors: Wittkowski Werner H , Schulze-Bonhage Andreas H , Böckers Tobias M
Published: June 2009

The pineal hormone melatonin is known to influence circadian systems. Melatonin is also ascribed to mediate photoperiodic effects on the regulation of the hypothalamo-hypophyseal-gonadal axis. Other endocrine actions, especially a thyrotropic influence, have been postulated. Site and mechanism of action of melatonin, however, are still matters of speculation. In search of a functional cascade of (i) photoperiodic stimuli, (ii) their hormonal messenger melatonin, and (iii) endocrine targets, the pars tuberalis has gained a key position. The recent discovery and characterization of melatonin receptors located in the pars tuberalis of several species support such a functional significance. Earlier results point to a functional connection of the pars tuberalis with the pineal gland: the pars tuberalis is known for a pattern of differentiation distinctly different from other parts of the adenohypophysis. It contains a specific cell population with a morphology typical of peptide secreting cells. Like the hypothalamic nerve endings of the median eminence, they are in close contact with the primary plexus of the portal system. In contrast to secretory cells of the pars distalis, the specific cells of the pars tuberalis do not respond with morphological alterations to functional changes of peripheral endocrine glands. Yet, photoperiodic stimuli obviously influence morphology and functional activity of the pars tuberalis-specific cells. Investigations during recent years have led to the tentative conclusion that the pars tuberalis represents the hypophysial "receptor"for melatonin as the chemical messenger of photoperiodic stimuli. Depending on melatonin secretion pattern and melatonin receptivity, the pars tuberalis seems to modulate at least gonadotropic and thyrotropic activity of the pars distalis via a peptide hormone distributed in the pars distalis by the portal plexus. Such an intrahypophysial regulatory concept may explain the widespread actions of melatonin on endocrine targets.
Increased lymphocyte thermogenesis in hyperthyroid patients. Role of Na/K pump function. Evaluation of aerobic/anaerobic metabolism
Authors: Valdemarsson Stig , Ikomi-Kumm Julie , Monti Mario
Published: June 2009

The role of the Na/K pump for the increased cell energy expenditure in hyperthyroidism was studied by measuring total lymphocyte heat production rate in samples with and without ouabain inhibition of Na/K ATP-ase. In addition, the relative contribution of aerobic processes to lymphocyte thermogenesis was calculated from oxygen consumption measurements. In 12 patients with clinical and laboratory hyperthyroidism total lymphocyte heat production rate was 3.19±0.21 pW/cell, significantly higher than in 7 patients with subclinical hyperthyroidism (2.14±0.11 pW/cell) and in 15 euthyroid subjects (2.26±0.11 pW/cell) (p<0.001). The relative decrease in lymphocyte heat production rate after ouabain, giving a quantitative measure of the activity of the Na/K ATP-ase and reflecting the importance of Na/K pump function for the overall rate of lymphocyte metabolism, was not significantly different between the groups: 19.5±3.6% in hyperthyroid patients, 14.2±2.3% in subclinical hyperthyroid patients and 17.8±3.1% in euthyroid subjects. According to the rate of lymphocyte oxygen consumption, aerobic processes represented 58.4±6.7% of total lymphocyte energy expenditure in hyperthyroid patients, not significantly different from subclinical hyperthyroidism (62.6±8.4%) or from euthyroidism (66.6±2.7%). These data do not support the hypothesis of a specific role of the Na/K pump function for the increased cell thermogenesis in hyperthyroidism and indicate a parallel stimulation of aerobic and anaerobic processes by thyroid hormone excess.