bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma 4-pregnene-17α,20α-diol-3-one (17α,20α-dihydroxyprogesterone) and 17α-hydroxyprogesterone in man
Authors: Whitworth Judith A. , Butkus Aldona , Coghlan J. P. , Denton D. A. , Saines Dianne , Scoggins B. A.
Published: December 2008

Investigation of the mechanisms involved in ACTH induced hypertension in sheep led to delineation of the major role of 4-pregnene-17α,20α-diol-3-one (17α,20α-OHP) in ovine adrenal venous blood. It has been shown in this model of steroid induced hypertension that 17α,20α-OHP is 'hypertensinogenic' i.e. capable of raising blood pressue when infused concurrently with the major mineralocorticoid and glucocorticoid steroid hormones, but in itself it has no significant blood pressure elevating effect and no significant glucocorticoid or mineralocorticoid activity. The present study examines the regulation of 17α,20α-OHP and 17α-hydroxyprogesterone (17-OHP) in man.

The plasma concentration of 17α,20α-OHP in normal ambulant subjects (n = 29) bled at 08.00 to 10.00 h was 14.5 ± 0.8 nmol/l compared with 17-OHP 7.8 ± 0.6 nmol/l. Administration of ACTH (20 μg/kg/day) to normotensive male subjects (n = 6) produced after 5 days of rise in 17α,20α-OHP from 16.6 ± 2.2 to 48.9 ± 7.9 nmol/l and in 17-OHP from 10.9 ± 1.12 to 29.3 ± 4.2 nmol/l. In normal subjects, 17α,20α-OHP had a diurnal rhythm similar to that of cortisol but of lower amplitude. Plasma concentrations of both steroids rose with stepped 30 min ACTH infusions and were suppressed by dexamethasone administration. Angiotensin II infusion, dietary sodium restriction and 9α-fluorocortisol administration had no effect on plasma 17α,20α-OHP. There was no change in 17α,20α-OHP throughout the menstrual cycle but 17-OHP increased during the luteal phase of the cycle. 17-OHP was lower in women on oral contraceptives than in control women, but values for 17α,20α-OHP were unchanged.

The mean plasma clearance rate for 17α,20α-OHP in 3 normal subjects was 30.2 l/day/kg, similar to that for aldosterone (31.2 l/day/kg). Unlike the sheep there was no in vitro conversion of 17-OHP to 17α,20α-OHP in human blood.

These studies show that 17α,20α-OHP is present in human plasma in higher concentration than 17-OHP. The secretion of 17α,20α-OHP appears to be primarily under the control of ACTH.
Loss of serum transcortin in human shock associated with severe infection by candida albicans
Authors: Zouaghi Hassen , Savu Lia , Delorme Jacqueline , Kleinknecht Dieter , Nunez Emmanuel A.
Published: December 2008

The cortisol binding ability of transcortin (corticosteroid binding globulin or CBG) was found to be virtually absent from the sera of patients in a state of shock associated with high levels of antibodies to candida albicans.

At the same time the serum proteins of the patients in shock displayed a number of the classical responses seen in acute inflammation: increased haptoglobin (28 ± 10 vs 10.8 ± 7.7 μm in normals), reduced prealbumin (1.7 ± 0.6 vs 3.6 ± 0.1 μm in normals) and albumin (485 ± 78 vs 600 ± 200 μm in normals).

The shock sera also showed increases in levels of endogenous cortisol (610 ± 260 vs 395 ± 192 nm in normals) and progesterone (2.40 ± 0.7 vs 1.4 ± 1.2 nm in normals) similar to those seen in inflammatory conditions.

In sera from patients with superficial chronic candidiasis no significant variation of cortisol binding was observed. Haptoglobin was increased (26.4 ± 8.2 μm) and pre-albumin decreased (2 ± 0.8 μm), while the other serum indices tested retained essentially normal levels.

Compared with previous studies from this laboratory which demonstrate a fall of CBG in septic shock of bacterial origin and lack of this response in acute inflammation, these results suggest that the loss of serum CBG acitivity is a specific marker for shock of fungal or bacterial aetiology.

Possible endocrine or immune implications and clinical applications of our findings are discussed.
Effect of a non-steroidal antiandrogen, flutamide, on the hypothalamo-pituitary axis, genital tract and testis in growing male rats: endocrinological and histological data
Authors: Viguier-Martinez M. C. , de Reviers M. T. Hochereau , Barenton B. , Perreau C.
Published: December 2008

Male Wistar rats were treated between 23 to 38 days of age with flutamide. Hypothalamic LRH content, pituitary gonadotrophin concentrations and plasma LH, FSH, Prl and testosterone levels were measured by radioimmunoassay.

The testis, epididymis and accessory organs were weighed and the histology of the testis, and the estimation of gonadotrophin receptors were performed in the same animals. The results were compared with data obtained in control animals of the same age. Flutamide treatment induced a direct inhibition of the genital tract. On the hypothalamo-pituitary axis, flutamide acted as a pure antiandrogen able to inhibit the negative feedback of testosterone, producing an increase in pituitary LH synthesis, as well as release of LH, FSH and Prl. The high level of plasma LH stimulated hyperplasia and hypertrophy of interstitial cells of the testis. Consequently testosterone synthesis was stimulated, although the number of LH receptor sites per Leydig cell was unchanged. Sertoli cells divisions were stimulated by the high level of gonadotrophins, but Sertoli cell function and the number of FSH receptors sites per Sertoli cell were slightly decreased. The increase in the number of type A spermatogonia and early stages of meiosis of primary spermatocytes could be related to the increase in plasma levels of FSH, whereas the drastic decrease in the late stages of spermatogenesis could result from the direct inhibition of testosterone by flutamide in the seminiferous tubules.
Prostaglandin F2α in blood plasma and milk of non-pregnant and pregnant buffaloes (Bubalus bubalis)
Authors: Batra S. K. , Pandey R. S.
Published: December 2008

Radioimmunoassay of prostaglandin F2α (PGF2α) was standardised for sufficient precision, accuracy, sensitivity and specificity. The changes of PGF2α were monitored in peripheral blood plasma and milk of 28 Murrah buffaloes. There were considerable individual variations of PGF2α concentration in blood plasma (27.6 to 110.8 pg/ml) and milk (80.3 to 180.4 pg/ml). A non-significant increase of PGF2α concentration (P > 0.05) was observed at the end of the cycle of non-pregnant animals in both fluids but no such increase was observed in pregnant animals. The concentration of PGF2α in milk was significantly higher (P<0.01) than that of blood plasma and was positively correlated in non-pregnant (r = 0.738) and pregnant animals (r = 0.385).
Changes of pituitary secretion after long-term treatment with hydergine, in elderly patients
Authors: Rolandi Ermanno , Magnani Gianni , Bottaro Luigi , Barreca Tommaso
Published: December 2008

The aim of this study was to evaluate the effects of long-term treatment with an ergot derivative, dihydroergotoxine mesylate (hydergine) 6 mg/day, on pituitary secretion on 10 elderly patients of both sexes. Samples were drawn at 120 min intervals during a 24 h period, before and after 1 month of therapy. Serum levels of Prl, GH, LH, FSH, TSH and cortisol were measured by RIAs. Hydergine induced a significant increase in the nocturnal serum GH peak. Conversely, no appreciable changes in the pattern of the other hormones studied were found. The observed endocrine effects could be due to the chronic dopaminergic stimulation induced by hydergine.
Influence of pulsatile administration of LRH on the development of the augmentative (positive) effect of oestradiol on the pituitary response to LRH
Authors: van Dieten J. A. M. J. , van Rees G. P.
Published: December 2008

Ovariectomized (OVX) rats were treated for 24 h with pulses of LRH (1.25 ng/100 g b.w. every 20 min) or of saline. Moreover, the animals received 3 sc injections of oestradiol benzoate (EB) (50 μg) or oil during this period. At the end of this period all animals received phenobarbital (80 mg/kg ip) and the animals were given pulses of LRH (once every 20 min) containing 1.25, 2.5, 5.0 or 10 ng for 3 h. Pulsatile administration of 1.25 ng pulses for 24 h did not lead to pituitary insensitivity. Treatment with EB caused the development of an increased response to LRH (positive effect). When during the 24–27 h period 5.0 or 10.0 ng pulses of LRH were given, the positive response was the same whether LRH had been administered during the 0–24 h period or not. However, the response to 2.5 ng pulses of LRH was halved when the animals had been pre-treated with LRH. It is concluded that the presence of LRH can inhibit partly the development of the positive pituitary response to LRH as caused by EB.

When the dose of LRH was kept at 1.25 ng/pulse no clear positive effect developed. Chronic administration of phenobarbital for 24 h caused pituitary insensitivity, presumably through a direct toxic effect.
Multiple species of FSH are present within hamster anterior pituitary cells cultured in vitro
Authors: Ulloa-Aguirre Alfredo , Coutifaris Christos , Chappel Scott C.
Published: December 2008

Anterior pituitary cells were obtained from ovariectomized hamsters and cultured for 4 days. The cells were lysed and intracellular proteins, including FSH, were separated by polyacrylamide gel isoelectric focusing. FSH present within cell lysates so separated was quantitated by a specific FSH radioimmunoassay (RIA). Six distinct species of intracellular FSH were observed with pI values = 5.9, 5.7, 5.3, 5.1, 4.7 and 4.3 – 3.8. All six species were detectable when proteins from a concentrate of incubation medium collected from those cell cultures were separated by isoelectric focusing. Similar isoelectric points were obtained when the FSH species present within an anterior pituitary homogenate obtained from ovariectomized hamsters were separated by the same technique. All but two of these six species of intracellular FSH were well recognized by a hamster FSH receptor preparation. However, these two species of FSH (pl values = 4.7 and 4.3 – 3.8) do not appear to be β subunits of the intact glycoprotein as determined by gel filtration. Thus, the present studies demonstrate that, as observed previously in anterior pituitary glands obtained from intact and castrated animals, pituitary cells that have been enzymatically dissociated and cultured in vitro for 4 days contain and secrete multiple species of FSH that are separable by polyacrylamide gel isoelectric focusing. This in vitro system may be useful for studying the hormonal factors that regulate FSH species synthesis and secretion.
Thyroid function in patients with proteinuria and normal or increased serum creatinine concentration
Authors: Adlkofer Franz , Hain Hannelore , Meinhold Harald , Kraft Dieter , Ramsden David , Herrmann Jörg , Heller Wolf-Dieter
Published: December 2008

The thyroid function of 13 patients with proteinuria and normal serum creatinine level (Group 1) and 15 patients with proteinuria and increased creatinine level (Group 2) was investigated. The daily urinary T41-and T3 excretion was much higher in Group 1 patients than in Group 2 patients (37.1 ± 25.9 nmol T4 vs 17.5 ± 8.7 nmol T4, 3.3 ± 1.6 nmol T3 vs 1.1 ± 0.8 nmol T3, respectively) and correlated in both groups with the protein loss. None of the patients suffered from hypothyroidism as a consequence of this hormone loss. Although the mean serum T4-, T3-, FT4-, FT3-, TBG-and TBPA concentrations in both groups of patients were within the normal range, the urinary hormone loss appeared to influence these values considerably. It was striking that the rT3 concentration in the patients with the highest hormone loss was frequently less than 0.08 nmol/l, the lower limit of detectability. The basal TSH levels in serum of the nephrotic patients were similar to those of normal individuals. The thyroid function of patients with proteinuria accompanied by retention of creatinine due to renal failure was more difficult to assess because different pathological mechanisms may exert their influence on the thyroidal hormone secretion as well as on the peripheral hormone metabolism.
Influence of age, strain and season on diurnal periodicity of thyroid stimulating hormone, thyroxine, triiodothyronine and parathyroid hormone in the serum of male laboratory rats
Authors: Wong Chun-Cheung , Döhler Klaus-D. , Atkinson Michael J. , Geerlings Heinz , Hesch Rolf-Dieter , von zur Mühlen Alexander
Published: December 2008

The influence of age, strain and season on the diurnal pattern of serum hormone levels from the pituitary-thyro-parathyroid complex was studied in male laboratory rats. Distinct 24 h periodicity in the serum levels of thyroid stimulating hormone (TSH) and triiodothyronine (T3) was observed in all groups of rats. There was no influence of age (40, 60 and 90 days old Sprague-Dawley rats), but a significant influence of strain (Sprague-Dawley vs. BH/Ztm rats) and season (summer vs. winter) on the diurnal pattern of serum TSH and T3 levels. Significant 24 h periodicity in serum thyroxine (T4) levels existed during winter in BH/Ztm rats, but not in Sprague-Dawley (SD) rats of any age. Adult SD rats demonstrated 24 h periodicity in serum levels of T4 only in summer. No diurnal periodicity in serum levels of parathyroid hormone (PTH) was observed in any group of rats.

There were significant changes in 24 h mean serum levels of TSH and T3 throughout pubertal development. Twenty-four h mean serum levels of T3 and T4 were significantly higher in summer than in winter. Twenty-four h mean serum levels of T4 were significantly lower in BH/Ztm rats than in SD rats. Significant correlation was observed between serum concentrations of T3 and T4, TSH and T4, and between TSH and T3 in some groups of rats, but not in all.

The results indicate that 24 h periodicity of serum hormone levels from the pituitary-thyroid complex of male laboratory rats may vary with age and strain of the animals and with the season of experiment performance.
Familial Cushing's syndrome due to pigmented multinodular adrenocortical dysplasia
Authors: Böhm N. , Lippmann-Grob B. , Petrykowski W. v.
Published: December 2008

Cushing's syndrome was diagnosed in a 14 year old girl and, 5 years later, in her nephew (sister's son) also when he was 14 years of age. Administration of tetracosactid (Synacthen®) did not stimulate adrenocortical function in either patient, nor did dexamethasone suppress the elevated urinary steroids in the girl, and only partially suppressed them in the boy. Both patients were adrenalectomized and made an uneventful recovery.

The surgical specimens were identical both on gross inspection and histologically, showing the typical morphological features of pigmented multinodular adrenocortical dysplasia.

We believe that this lesion represents an inherited adrenocortical maldevelopment (rather than true neoplasia) leading to an autonomous adrenocortical hyperfunction which typically manifests itself clinically during adrenarche (i.e. functional adrenocortical maturation) at the beginning of puberty. Familial Cushing's syndrome, caused by pigmented multinodular adrenocortical dysplasia, represents a disease entity.
A double-blind cross-over study on the effects of ORG OD14 compared to oestradiol valerate and placebo on lipid and carbohydrate metabolism in oophorectomized women
Authors: Crona N. , Silfverstolpe G , Samsioe G.
Published: December 2008

ORG OD14 is a synthetic steroid which in traditional bioassays has been shown to have oestrogenic and progestogenic as well as very weak androgenic-anabolic properties. As judged from earlier studies, this steroid seems suitable for continuous treatment of climacteric deficiency symptoms. The aim of this study was to evaluate the effects induced by OD14 on lipid, lipoprotein and carbohydrate metabolism, as compared to E2V and placebo.

Twenty-two women, oophorectomized as part of the treatment of cervical carcinoma in clinical stage IB or IIA, were given ORG OD14 2.5 mg/day, oestradiol valerate (E2V) 2 mg/day and a placebo for 6 weeks each, in a double-blind cross-over study.

There was a marked decrease in all lipid components of HDL (high density lipoprotein), i.e. total and free cholesterol, triglycerides and phospholipids (P < 0.001), after OD14. The oral glucose tolerance test showed higher values after OD14 compared to both E2V and placebo (P < 0.05), indicating a slightly impaired glucose tolerance. The lipid metabolic changes induced by OD14 indicate a rather strong androgenic influence in this respect.
Saliva and serum testosterone following oral testosterone undecanoate administration in normal and hypogonadal men
Authors: Schürmeyer Th. , Wickings E. J. , Freischem C. W. , Nieschlag E.
Published: December 2008

Since saliva testosterone reflects the testosterone fraction available to target tissues the therapeutic effectiveness of orally administered testosterone undecanoate was assessed by measuring testosterone in serum and saliva. Matched saliva and serum samples were obtained from 12 normal men and 8 hypogonadal men before and at hourly intervals after the oral administration of 120 mg testosterone undecanoate. The test was repeated in 3 men after they had taken 40 mg testosterone undecanoate twice daily for 4 to 5 weeks.

Following testosterone undecanoate administration serum and saliva testosterone always showed parallel increases. However, the absorption curves showed a high interindividual variability in the time when maximum concentrations were reached, as well as in the maximum levels themselves. The increases in serum and saliva testosterone were similar in normal and hypogonadal men. In normal men basal levels were reached 4 h after the maximum had occurred, while in hypogonadal men testosterone levels were not different from basal levels 2 h after the maximum. The study shows that testosterone undecanoate is well absorbed from the gut and releases significantly elevated amounts of testosterone which is available to target tissues. As the absorption pattern was always parallel in both fluids, hydrolysis of the circulating testosterone ester by the tissue ifself seems to effect no additional increase of testosterone in the tissue.
Prolactin release in man: influence of cimetidine, thyrotrophin-releasing hormone and acute hypercalcaemia
Authors: Röjdmark Sven
Published: December 2008

The responsiveness of anterior pituitary lactotrophs and thyrotrophs to cimetidine (Cim) was investigated in healthy volunteers. Four-hundred mg Cim, injected iv, raised the serum prolactin level (Prl) from 14 ± 2 to 58 ± 9 ng/ml (P < 0.001), but left the serum thyrotrophin level (TSH) unaffected. Acute hypercalcaemia, induced by iv infusion of calcium, blunted this Cim-elicited Prl response by 35 ± 4% (P < 0.01). Iv injection of 25 μg thyrotrophin-releasing hormone (TRH) had similar Prl-releasing potency as 400 mg Cim, and raised the Prl level from 14 ± 1 to 51 ± 6 ng/ml (P < 0.001). In contrast to Cim, TRH also increased the TSH level significantly. Although oral pre-treatment with Cim for 3 days (1000 mg/day) failed to affect the Prl response to TRH in this study, iv injection of the drug more than doubled the above mentioned Prl response to TRH. The TSH response to TRH remained unaffected both by oral and by iv administration of Cim. These results imply that acute changes in serum calcium affect the release pattern of Prl, and that iv administration of Cim may add Prl-releasing power to TRH in healthy individuals.
Androgenic and oestrogenic steroid participation in feedback control of luteinizing hormone secretion in male sheep
Authors: D'Occhio M. J. , Schanbacher B. D. , Kinder J. E.
Published: December 2008

The acute castrate ram (wether) was used as an experimental model to investigate the site(s) of feedback on luteinizing hormone (LH) by testosterone, dihydrotestosterone and oestradiol. At the time of castration, wethers were implanted subdermally with Silastic capsules containing either crystalline testosterone (three 30 cm capsules), dihydrotestosterone (five 30 cm capsules) or oestradiol (one 6.5 cm capsule). Blood samples were taken at 10 min intervals for 6 h 2 weeks after implantation to determine serum steroid concentrations and to characterize the patterns of LH secretion. Pituitary LH response to exogenous LRH (5 ng/kg body weight) were also determined at the same time. The steroid implants produced serum concentrations of the respective hormones which were either one-third (testosterone) or two-to-four times (dihydrotestosterone, oestradiol) the levels measured in rams at the time of castration. Non-implanted wethers showed rhythmic pulses of LH (pulse interval 40–60 min) and had elevated LH levels (16.1 ± 1.6 ng/ml; mean ± se) 2 weeks after castration. All three steroids suppressed pulsatile LH release and reduced mean LH levels (to below 3 ng/ml) and pituitary LH responses to LRH.

Inhibition of pulsatile LH secretion by all three steroids indicated that testosterone as well as its androgenic and oestrogenic metabolites can inhibit the LRH pulse generator in the hypothalamus. Additional feedback on the pituitary was indicated by the dampened LH responses to exogenous LRH.
Prolactin release induced by stress and the influence of oestrogen and progesterone treatments, sex and daily rhythm
Authors: Caligaris L. , Taleisnik S.
Published: December 2008

The effect of sex, ovarian steroids and time of the day on the release of prolactin induced by stress was studied. Albino rats were bled by heart puncture and immediately anaesthetized with ether; 10 min later they were bled again. Ovariectomized, oestrogen-primed rats showed a daily rhythm in the stress (bleeding plus ether) induced prolactin release with maximal concentration of prolactin in the serum at night (01.00 h) and minimum in the morning (09.00 h). In ovariectomized, oestrogen-treated rats the rise of prolactin in the serum after stress was higher than in the non-treated rats both in the morning and at night. However in the afternoon (17.00 h), when the pre-stress levels of prolactin were high, the response to stress was reversed and prolactin levels declined. A similar effect was seen in the ovariectomized, oestrogen-primed rats 4 h after the injection of progesterone. In these animals the concentration of prolactin in serum was high and declined after stress. However 28 h after injection of progesterone stress failed to induce any change in prolactin release. Progesterone injected into ovariectomized, non-primed rats did not influence the response to stress. In male rats, both intact and castrated, the increase of prolactin concentration in serum after stress was lower than in females and failed to exhibit a circadian rhythm.

These results show the importance of the hormonal background and the time of the day in the magnitude of prolactin release induced by stress.
Oxytocin and renal function in the rat; an investigation of a possible proximal site of action
Authors: Garland H. O. , Balment R. J. , Brimble M. J.
Published: December 2008

Direct measurements of proximal tubular fluid reabsorption have been employed to examine the possible renal site of action of oxytocin. In whole kidney studies the natriuresis and chloriuresis, which occurred during the period of oxytocin infusion, did not coincide with the associated diuresis. The latter reached a peak 10–20 min after hormone administration has ceased. The separation in the saliuretic and diuretic responses underlines the apparent independence of these actions of oxytocin on the renal handling of water and electrolytes. The disturbances in renal function were not related to any change in glomerular filtration rate (gfr) and an examination of single nephron function failed to detect any significant effect of oxytocin on proximal tubular reabsorption. The renal actions of oxytocin would therefore appear to emanate from altered tubular rather than glomerular function, though the present study provides no support for a proximal site of action.
Calcitonin increases calcium content and glucose-6-phosphatase activity in hepatic microsomes of rats
Authors: Yamaguchi Masayoshi , Momose Kaoru
Published: December 2008

The effect of calcitonin (CT) on calcium content and glucose-6-phosphatase activity in the hepatic microsomes of rats was investigated. A single sc administration of CT (80 MRC mU/100 g body weight) produced a significant increase in microsomal calcium content and a corresponding elevation of microsomal glucose-6-phosphatase activity. An appreciable effect of CT was observed at a dose of 20 MRC mU/100 g body weight. On the other hand, the removal of calcium by 10 mM EGTA washing of the microsomes caused a marked reduction of glucose-6-phosphatase activity raised by CT administration. The addition of calcium ion at the amount of 10−2– 103 nmoles Ca2+ per mg protein in the microsomes produced a significant increase in glucose-6-phosphatase activity. The present results suggest that microsomal calcium increased by CT administration activates glucose-6-phosphatase in the hepatic microsomes of rats.
In vivo and in vitro effects of metoclopramide on aldosterone secretion in rats
Authors: Nagahama Shusaku , Fujimaki Masaki , Suzuki Hiroko , Kawabe Hiroshi , Saito Ikuo , Saruta Takao
Published: December 2008

This study was designed to investigate the effects of metoclopramide, a dopamine antagonist, on in vivo and in vitro aldosterone production in the rat. In addition, we examined the effect of various levels of sodium intake on the response of plasma aldosterone to metoclopramide.

Metoclopramide (2–50 mg/kg) was given by ip injection to conscious rats. Metoclopramide induced a dose-related increase in plasma aldosterone, whereas it only increased plasma renin activity at high doses (20 and 50 mg/kg). The response of plasma aldosterone to 10 mg/kg of metoclopramide in the low-sodium group was greater than that in the high-sodium group.

Metoclopramide had no effect on aldosterone production in isolated zona glomerulosa cells in vitro.
Effect of agonists and antagonists of cholinergic neurotransmission on growth hormone release in the dog
Authors: Casanueva Felipe F. , Betti Roberto , Cella Silvano G. , Müller Eugenio E. , Mantegazza Paolo
Published: December 2008

Abstract. In unanaesthetized dogs iv administration of the cholinesterase inhibitor eserine (0.5 mg) or the cholinergic muscarinic receptor agonist oxotremorine (0.25 mg) induced a clear-cut rise in plasma canine growth hormone (cGH) levels. Complete suppression of the GH-releasing effect of eserine and oxotremorine was induced by blockade of cholinergic muscarinic receptors by atropine (80 or 20 μg/kg, 30 min before) but not by scopolamine-N-butyl bromide (0.8 mg/dog, 30 min before), an anticholinergic drug which does not cross the blood brain barrier (BBB). In contrast, activation of cholinergic nicotinic receptors by nicotine (6 mg) failed to alter resting cGH concentrations, and pre-treatment with the nicotinic receptor blocker mecamylamine (5 mg, 30 min before) did not counteract the GH-releasing effect of eserine. Other cholinomimetic drugs, e.g. pilocarpine, 4-aminopyridine, carbachol and bethanechol failed to induce a rise in plasma cGH concentrations. These data indicate that: 1) cholinergic muscarinic but not nicotinic receptors located in the central nervous system (CNS) inside the BBB play a facilitatory role in tonic cGH release; 2) pharmacologically distinct muscarinic receptors may exist in the CNS.
TSH-regulation and goitrogenesis in severe iodine deficiency
Authors: Bachtarzi H. , Benmiloud M.
Published: December 2008

Abstract. Since goitre prevalence increases sharply during the first two decades of life, age-related changes in the adaptation of the thyroid to iodine deficiency may occur. In order to study this, we have measured serum levels of TSH, T4 and T3 in 247 subjects (age range 5 to 60 years) living in an endemic goitre area of North Algeria (group A) and in 64 control subjects living in the non-iodine deficient city of Algiers (group B). TRH tests were also performed in 88 subjects from the goitrous area and in 30 controls.

Patients from group A had significantly higher serum TSH and T3 and lower serum T4 than those from group B. Analysis of group A by age groups revealed significantly higher TSH concentrations in the 2–9 years group and a moderate but significant decrease in the group from 50–59 years. No significant changes were demonstrated for T4 and T3.

In the goitrous area, the response of TSH to TRH was exaggerated and prolonged. ΔTSH20 was inversely correlated with age. The different age groups showed a significantly progressive and continuous decrease of ΔTSH20, ΔTSH60, ΔTSH120 from age 10–19 to age 50–59 years.

Our findings thus show a sharp increase of TSH during the first decades of life, which coincides with the phase of maximal growth of the thyroid gland. These results suggest that TSH plays a definite role in the genesis of endemic goitre. The subsequent progressive decrease of TSH secretion and reserve, with unchanged T4 and T3, imply a gradual development of autonomous activity in longstanding multinodular goitre.
Intralysosomal hydrolysis of thyroglobulin
Authors: Fouchier Francis , Mego John L. , Dang Josseline , Simon Claude
Published: December 2008

Abstract. Intralysosomal hydrolysis of endogenous (125I in vivo labelled) thyroglobulin (Tg) inside thyroid phagolysosomes and its modulation by exogenous factors (external pH, activators and inhibitors of lysosomal proteinases) were studied during in vitro incubations. Tg degradation was followed as the time-dependent increase in TCA-soluble radioiodine (free iodoaminoacids).

The results demonstrate that this hydrolysis is only partially pH-dependent, one component being abolished by pH 8 and a cathepsin B inhibitor (zinc) whereas the residual activity was pH-independent and insensitive to zinc. It would seem therefore that the total thyroid phagolysosome population contains lysosomes permeable to both incubation buffer and zinc and lysosomes impermeable to these compounds. Both classes are operational (degrade Tg) at acidic or neutral pHs, while only impermeable organelles function when incubated at pH 8. These impermeable lysosomes have an acidic internal pH (about pH 5) and resist alkalinization very efficiently due to the high impermeability of their membranes. Additional experiments are in progress to determine the physiological significance of these two classes of lysosomes which might be related to a functional maturation of thyroid phagolysosomes.
Intralysosomal hydrolysis of thyroglobulin
Authors: Fouchier Francis , Mego John L. , Dang Josseline , Simon Claude
Published: December 2008

Abstract. Degradations of recently (1 h) iodinated thyroglobulin (Tg) and of Tg iodinated for 48 h (fully iodinated molecule) inside thyroid phagolysosomes have been measured in vitro, at different pH, in basal (lysosomes from normal rats) and stimulated (lysosomes from TSH-treated rats) conditions.

In basal conditions, recently iodinated Tg was shown to be preferentially degraded at pH 5 but not at pH 8. Mercaptoethanol (ME) was found to preferentially stimulate the degradation of 48 h-iodinated Tg at pH 5 but not at pH 8.

In stimulated conditions and in the presence of ME, no preferential hydrolysis of recently iodinated Tg was observed, whatever the pH.

Since the degradation of Tg and its stimulation by ME are known to depend on the mean iodine content of the molecule, it was concluded that: 1) the recently iodinated Tg population contains both poorly and fully iodinated molecules, the degradations of which are faster or similar to that of 48 h-iodinated Tg, respectively, 2) among thyroid phagolysosomes, only those which exhibit a pH-dependent proteolytic activity contain poorly iodinated molecules while others, which are functional at either pH, contain solely fully iodinated molecules (1 and 48 h labelled), 3) reduction of the disulphide bridges of fully iodinated Tg, mediated by ME and probably a lysosomal transhydrogenase, is a prerequisite for its optimal degradation by lysosomal proteinases, 4) in addition, TSH, which preferentially stimulates the degradation of fully iodinated Tg, was concluded to interfere directly upon the intralysosomal hydrolytic process, independently of its effect upon Tg endocytosis. This effect of TSH, similar and additive to that of ME suggests that the hormone might activate a lysosomal transhydrogenase.
A non-surgical technique for the transcervical administration of physiological and pharmacological agents into rat uteri
Authors: Chwalisz Krzysztof , Zou Ji-Chao , Jungblut Peter W.
Published: December 2008

Abstract. A technique for the instillation of solutions into the rat uterine lumen is described. The method has been tested by following the receptor depletion/replenishment cycle after oestradiol injection and by checking on the stoichiometry of hormone/receptor translocation from the cytoplasmic compartment into the nucleus. Both crude sediments from frozen uteri and nuclei purified by a novel procedure were analyzed and gave identical results. The limitations and the advantages of the technique are discussed.
Antibody production against an agonist analogue of luteinizing hormone-releasing hormone: evaluation of immunochemical and physiological consequences
Authors: Fraser H. M. , Sandow J. , Krauss B.
Published: December 2008

Abstract. Because of the widespread long-term clinical use of luteinizing hormone-releasing hormone (LRH) agonists, the possibility of antibody development to one of these, (D-Ser-(Butt)6) LRH (1–9) nonapeptide-ethylamide (buserelin), has been studied by examining sera from experimental animals and humans receiving long-term agonist-treatment for ability to bind 125I-labelled buserelin. None of the sera from monkeys, rabbits, dogs or rats receiving buserelin by sc injection or via minipump or from 81 patients receiving the agonist by sc injection or nasal spray had detectable antibodies.

The immunochemistry of buserelin was investigated by actively immunizing male rabbits against the agonist. This also enabled us to determine the possibility of this stimulus to the immune response resulting in the generation of antibodies which could cross-react with endogenous LRH and neutralize its biological effect.

All 41 rabbits immunized against unconjugated buserelin and all 23 immunized against buserelin conjugated to a protein carrier developed antibodies, those in the latter group producing highest titres. Serum from one of the animals immunized against unconjugated buserelin and from 9 of the animals immunized against conjugated buserelin had the capacity to bind 125I-labelled LRH. These LRH antibody titres were very low and were insufficient to cause suppression of serum testosterone concentrations or affect testicular weight except in one rabbit immunized against unconjugated agonist. The LRH antibody titre in this rabbit was always < 1:100 which our other studies have indicated to be too low to produce a biological effect. It may be that the association of low LRH antibody titre with decreased testes weight in this animal was fortuitous.

We conclude that the possibility of circulating antibodies being produced to buserelin or their interfering with the action of endogenous LRH is extremely low.
Partial purification and properties of the TSH receptors from human thyroid plasma membranes
Authors: Iida Yasuhiro , Konishi Junji , Kasagi Kanji , Endo Keigo , Misaki Takashi , Kuma Kanji , Torizuka Kanji
Published: December 2008

Abstract. Human thyroid plasma membranes were solubilized with 0.5% Triton X-100 and TSH receptors were purified by using DEAE-Sephadex, Con A and TSH affinity chromatography.

A TSH binding activity was bound to DEAE-Sephadex equilibrated with 0.05 m sodium acetate, pH 6.3, 0.2% Triton X-100 and was eluted by a linear gradient of 0.1 m to 1.0 m ammonium acetate, pH 6.3. Eighty-five per cent of the activity was absorbed to Con A Sepharose and was eluted with 0.5 m α-methyl-D-mannoside, 0.05 m sodium acetate, pH 6.0. Seventy-five per cent of the TSH binding capacity could be absorbed to TSH-affinity column and was eluted with 0.1 m glycine-HCl, pH 3.0.

By sequential application of the above procedures, more than 100-fold purification of the receptor activity was attainable. [125I]TSH binding of this fraction was inhibited by addition of unlabelled TSH in a dose-dependent manner. Scatchard analysis gave a curvilinear plot with a high affinity association constant of 0.72 × 109 m−1. By using Ultrogel AcA 34 gel filtration, the molecular size of the hormonereceptor complex was estimated to be 180 000.
Suppression and stimulation of TSH and thyroid hormones in bulls during starvation and refeeding
Authors: Tveit Borghild , Larsen Flemming
Published: December 2008

Abstract. Sixteen bull calves were fasted during two periods, 3½ and 7 months old. Blood samples were taken every 6 h during an experimental period of 9 days: 2 control days, 5 fasting days and 2 refeeding days.

During the control days with ad libitum feeding, T3, T4 and TSH increased during the day. During the fasting period, T4 decreased with a half-life of 3.5 days and T3 with a half-life of 3 days. TSH decreased in a less regularly way to a mean of 60% of control mean. Six h after refeeding, TSH had increased to 300% of control mean. T3 and T4 had a maximum 12 h after refeeding.

As the T4 decreased with a rate nearly similar to the T4 disappearance rate in starving bulls, the secretion of T4 from the thyroid gland must have been almost stopped during the starvation period.

The morning values were below normal for all three hormones after 2 days of refeeding.
Thyroglobulin-rich colloid goitres: a result of the combined action of lithium and methimazole on the rat thyroid
Authors: Miloni E. , Bürgi H. , Studer H. , Siebenhüner L. , Lemarchand-Béraud Th.
Published: December 2008

Abstract. Naturally occurring euthyroid goitres in man and goitres produced in experimental animals by iodine deficiency or goitrogen feeding both have in common a thyroglobulin of low iodine content. The latter experimental goitres are always depleted of colloid and thyroglobulin. In contrast, natural goitres often contain excessive amounts of colloid which may accumulate because of endocytosis becoming refractory to TSH. We tested the hypothesis that minute doses of goitrogens could lower the iodine content of thyroglobulin without colloid depletion. We then examined whether such a low-dose 'classical' goitrogen could induce excessive colloid storage rather than depletion if acting in concert with lithium, a cation which blocks endocytosis.

Rats on an adequate iodine intake were fed minimal doses of methimazole either alone or combined with lithium chloride. Chronic minimal-dose methimazole treatment lowered the iodine content of thyroglobulin without changing thyroglobulin content and thyroid weight. In contrast, addition of lithium to methimazole, produced goitres containing supranormal amounts of poorly iodinated thyroglobulin. We conclude that borderline doses of goitrogens can lower iodination of thyroglobulin without causing hyperplasia and colloid depletion. Thyroglobulin-rich goitres can be obtained by adding a second goitrogen which inhibits endocytosis. As an alternative to Marine's hypothesis of colloid goitre formation we suggest that inhibition of endocytosis, e g by goitrogens of the lithium type, could cause colloid and thyroglobulin accumulation in human iodine deficiency goitre.
Effect of a hypoglycaemic sulphonylurea (HB419) and a non-metabolizable amino acid (BCH) on the insulin release and endogenous substrate metabolism of rat pancreatic islets
Authors: Khatim Mohamed S. , Gumaa Khalid A. , Hallberg Anders , Eriksson Ulf , Hellerström Claes
Published: December 2008

Abstract. The effects of the hypoglycaemic sulphonylurea glibenclamide (HB419) and the non-metabolizable leucine analogue β-2-aminobicyclo(2.2.1)heptane-2-carboxylic acid (BCH) on insulin release and endogenous substrate metabolism were studied in isolated rat islets. Pre-labelling of the endogenous islet substrates was performed with [14C]glucose (20 mm) or [14C]glutamine (10 mm) during a 24 h tissue culture period before measurements of insulin release or 14CO2 production in short-term incubations. Both HB419 and BCH stimulated the insulin release of the cultured islets, although BCH only after culture of islets with glutamine. The rate of labelling of the islets with [14C]glucose reached an apparent plateau after 16 h in culture and the total islet accumulation of glucose carbon over the 24 h period averaged 12.9 ± 3.0 nmol/25 islets. Less than 0.5% of the glucose residues was converted to glycogen whereas lipids represented about 2.5%. Fractionation of lipids showed 67% phospholipids, 18% triacylglycerols, 11% diacylglycerols and 6% non-esterefied fatty acid. The islet accumulation of glutamine during 24 h corresponded to 11.5 ± 1.5 nmol/25 islets.

After pre-labelling of islets with [14C]glucose there was no effect on the 14CO2-evolution over a 30 min incubation period of either HB419 or BCH. There was also no effect of HB419 after pre-labelling with [14C]glutamine, whereas, in this latter situation, a significant stimulation was observed with BCH. It is concluded that the effects on the pancreatic B-cells by antidiabetic sulphonylureas are not mediated via nutrient receptors.
Blood flow in the ovary and adjacent structures of the non-pregnant sheep
Authors: Janson P. O. , Williams D. , Petrucco O. M. , Amato F. , Seamark R. F. , Findlay J. K.
Published: December 2008

Abstract. Blood flow to the ovary, vascular pedicle and oviduct was measured in anaesthetized non-cycling and cycling ewes by timed collection of ovarian venous blood. The degree of arterio-venous shunting across the ovary and pedicle was estimated both in vivo and in vitro by perfusing the tissues with 15 ± 5 μm radioactive microspheres.

The mean ovarian blood flow in non-cycling animals was 1.9 ml/min, which was 51% of blood flow in the ovarian vein. In cycling animals ovarian blood flow at midcycle was 2.9 ml/min (66% of ovarian venous flow) in non-luteal ovaries and 4.3 ml/min (79% of venous flow) in luteal ovaries. The degree of arterio-venous shunting was low in all stages of the cycle (1.0–2.6% across ovary + pedicle). The degree of shunting was also found to be very small in vitro (0.007–1.38%) in both non-luteal and luteal ovaries. A considerable number of microspheres was entrapped in the vascular pedicle of the ovary indicating the presence of an extensive capillary bed. There was an inverse relationship between blood flow in the ovary and flow in the vascular pedicle.

Alterations in distribution of blood flow between the ovary and adjacent structures supplied by the ovarian artery may be of functional significance in allowing rapid changes in ovarian blood flow. The results of the present study indicate that changes in ovarian blood flow during the oestrous cycle are not caused by an action on arteriovenous shunt vessels.
Effect of starvation on gonadotrophin secretion and on in vitro release of LRH from the isolated median eminence of the male rat
Authors: Warnhoff Michael , Dorsch Gunter , Pirke Karl M.
Published: December 2008

Abstract. A perfusion system was developed in which isolated median eminences (ME) were stimulated in vitro by depolarizing agents such as potassium and veratridine. Potassium concentrations between 30 and 80 mm released increasing amounts of luteinizing hormone-releasing hormone (LRH) from the MEs of starved and control rats. Veratridine at a concentration of 50 μm caused a more prolonged LRH release in both starved and control animals. LRH secretion in vitro was slightly, though not under all conditions, significantly greater in rats starved for 5 days.

The testosterone (T)-LH feedback was studied by castrating the animals and substituting various doses of T through implantation of T-releasing capsules of different sizes. The concentration in plasma, which can prevent the castration-induced much smaller in starved than in control rats. The in vitro release of LRH evoked by 80 mm potassium was not different for starved and fed rats under various feedback conditions. Both groups revealed decreased in vitro release of LRH when castrated animals were not substituted with T.

The effect of castration was studied from 1 to 28 days. The plasma LH values rapidly increased in starved and control animals, indicating that the hypothalamic responsestration is not delayed by starvation. The release in vitro of LRH decreased from the first to the fifth day and remained constant thereafter. No significant difference between starved and fed rats was observed. The experiments indicate that the 'releasable pool' of LRH in vitro is greater under conditions of reduced LH release in vivo. The basic mechanism of depolarization-induced exocytosis of LRH from the ME is intact in starved animals.
Skeletal changes following growth hormone treatment in a child with combined hypopituitarism and a skeletal dysplasia
Authors: Horton William A. , Howard Campbell P. , Grunt Jerome A.
Published: December 2008

Abstract. A child with combined hypopituitarism and an undefined skeletal dysplasia is described. The hypopituitarism was manifested by post-natal growth failure, excessive sc fat, micropenis, and poor growth hormone response to provocative tests. Disproportionately short limbs, especially distally, and skeletal radiographs showing generalized brachydactyly, cone epiphyses of the phalanges and ossification defects in the proximal femoral metaphyses characterized the skeletal dysplasia. In contrast to the normal structure of the endochondral growth plate seen in hypopituitarism, the growth plate in this child was structurally abnormal; there was no differentiation of chondrocytes into hypertrophic and degenerative cells. Treatment with hGH for 8 months was associated with the appearance of chondrocyte differentiation, the restoration of growth plate structure to almost normal and a substantial increase in growth rate. There was no change in his disproportion or improvement in his radiographic abnormalities. These observations suggest that hGH may influence growth plate structure in certain instances and that this may be associated with increased linear growth.
Effects of a single oral dose of phenobarbital on prolactin, growth hormone and luteinizing hormone in normal women
Authors: Rosadini G. , Masturzo P. , Rodriguez G. , Murialdo G. , Montano V. , Bonura M. L. , Polleri A.
Published: December 2008

Abstract. The effects of a single oral dose of phenobarbital (PB) on the 24 h secretion of prolactin, growth hormone and luteinizing hormone have been evaluated in normal women. An EEG record was taken and barbiturate levels assayed in serum. A statistically significant decrease of growth hormone 24 h mean levels was observed and growth hormone and prolactin values during sleep were diminished. No changes in luteinizing hormone concentrations were observed. After PB the EEG showed no important alterations in sleep pattern, but on the power analysis an increase above 16 Hz absolute power was detected during the waking period.
Lack of effect of chronic hypocalcaemia on serum prolactin response to chlorpromazine
Authors: Usman Aydan
Published: December 2008

Abstract. The effects of chronic hypocalcaemia on serum basal and chlorpromazine-stimulated prolactin (Prl) levels were studied in 16 patients with idiopathic or secondary hypoparathyroidism. These results were compared with the results of other chlorpromazine stimulation tests which were made in the normocalcaemic state after treatment with vitamin D, and in normal subjects.

In hypocalcaemic and normocalcaemic states (mean serum Ca 5.8 ± 0.24 mg/dl and 9.5 ± 0.11 mg/dl, respectively) basal Prl levels were within the normal range and during stimulation the maximal stimilated levels in each state were not significantly different from each other. Also, the mean serum Prl levels obtained from a control group were not different from values in the normocalcaemic state.

It is concluded that chronic hypocalcaemia does not inhibit Prl secretion and low serum parathyroid hormone levels do not affect basal and chlorpromazine-stimulated Prl secretion.