bluuebunny/crossref_metadata_2025 huggingface dataset:
Human pituitary chronoendocrinology: repetitive stimulation with LRH/TRH at different times of the day
Authors: Pérez-López F. R. , Legido A. , Abós M. D. , Lafarga L.
Published: December 2008

To determine whether human pituitary is characterized by a circadian periodicity in response to repetitive injection of hypothalamic hormones, 8 healthy subjects were challenged iv with a triple stimulation with 50 μg of LRH and 100 μg of TRH in a single bolus at 0, 90 and 180 min, receiving the first pulse of hypothalamic hormones either at 02.00 h (02.00 h test) or at 09.00 h (09.00 h test). In addition, a placebo was injected instead of LRH/TRH to evaluate the spontaneous hormonal changes during the 02.00 h test.

The LH, FSH, Prl and TSH basal levels were similar in the two phases studied. The mean LH, FSH and TSH peaks after each injection of LRH/TRH were similar among them. The mean Prl peak responses to the third pulse of LRH/TRH, in both the 02.00 h and the 09.00 h tests, were lower (P < 0.05) than those after the first pulse of LRH/TRH. Placebo did not significantly change circulating LH, FSH, Prl or TSH during nocturnal sampling. The mean LH, FSH and Prl levels after LRH/TRH during the 02.00 h test were similar to those during the 09.00 h test. The mean TSH levels 15 min after the second and third pulses of LRH/TRH during the 02.00 h test were higher (P < 0.05) than those of the 09.00 h test.

Thus, thyrotropes responsiveness to pulsatile stimulation with LRH/TRH is greater during the night than in the morning, while LH, FSH and Prl responses remain constant at the two phases studied.
TSH unresponsiveness, a case report
Authors: Aarseth Hans Petter , Haug Egil , Raknerud Nils , Frey Harald M.
Published: December 2008

A patient with congenital primary hypothyroidism is presented. His thyroid gland had a normal uptake of radioiodine which was independent of endogenous or exogenous TSH, sympathetic B-receptor blockade or prostaglandin inhibition. Infusion of dibuturylcyclic AMP increased the uptake of radioiodine and stimulated release of protein bound 131I. He had no goitre even when he did not receive thyroxine, but thyroid histology showed evidence of active epithelium in the presence of adequate substitution with thyroxine. We assume that some unknown factor other than TSH stimulates part of the glandular function in this patient, without leading to adequate formation and release of thyroid hormone.
Further support for heterogeneity of insulin response and insulin sensitivity in non-obese subjects with glucose intolerance
Authors: Ratzmann K. P. , Witt S. , Schulz B.
Published: December 2008

The relationship of insulin secretion and insulin sensitivity was studied in 67 age- and body weight-matched non-obese subjects, classified as having a normal glucose tolerance or glucose intolerance (50 g oral glucose load). Insulin response was studied by means of a 2 h glucose infusion. For the determination of insulin sensitivity a 1 h priming dose-constant insulin infusion technique was used. The per cent decrease of plasma glucose level at comparable steady-state insulin levels served as a measure of body sensitivity to exogenous insulin. In patients with glucose intolerance the early (ΔIRI area 0–5 min) and late (ΔIRI area 30–120 min) insulin responses to iv glucose were significantly reduced in comparison to controls. Controls and subjects with glucose intolerance showed considerable heterogeneity of insulin responses. Patients with glucose intolerance and relative insulin deficiency were not less responsive to insulin than subjects with normal glucose tolerance. There was, however, a wide variation of insulin sensitivity within the two groups. There was a weak significant inverse correlation between insulin response to glucose and insulin sensitivity for the two groups combined and for controls and subjects with glucose intolerance separately. The results demonstrate that the majority of non-obese patients with glucose intolerance and relative insulin deficiency does not exhibit a reduced responsiveness to insulin and therefore hypoinsulinaemia but not insulin resistance is the primary defect for an abnormal glucose tolerance in these group of subjects.
Hepatic extraction of insulin after carbohydrate hyperalimentation
Authors: Olsen Margrethe E. , Faber Ole K. , Binder Christian
Published: December 2008

Peripheral venous plasma insulin and C-peptide concentrations during oral glucose tolerance tests were measured in 7 normal weight non-diabetic subjects before and after 7 days of sucrose hyperalimentation. This induced a deterioration of the glucose tolerance with higher levels of glucose, insulin and C-peptide.

The C-peptide to insulin molar ratio as well as the relation between incremental areas under the plasma curves of the two peptides were used as relative measures of the hepatic insulin extraction.

Both estimates of hepatic insulin extraction were unchanged by hyperalimentation, suggesting that the induced decreases in glucose tolerance and insulin receptor function are not followed by a decrease in hepatic insulin extraction as found in obese subjects with similar changes in glucose tolerance and insulin receptor function.
The renin-angiotensin system in association with hyperreninaemic hypoaldosteronism in neoplasia induced hypercalcaemia
Authors: Sowers J. R. , Barrett J. D.
Published: December 2008

The renin-angiotensin system was examined in Fischer rats at 7, 11 and 14 days after Leydig cell tumour transplantation and in age matched controls. Mean arterial blood pressure (MAP), active plasma renin and serum calcium were higher (P < 0.01) in the tumour transplant rats than in the controls at 11 days after transplantation. There was a positive correlation of both active renin and MAP with serum calcium at this time. Although inactive renin levels were elevated in the tumour transplanted rats, the ratio of inactive to active renin was decreased in comparison to controls. Plasma norepinephrine, active renin and plasma angiotensin II were higher in tumour rats at 14 days. Nevertheless, basal levels of aldosterone and MAP as well as aldosterone responses to graded infusion of angiotensin II, ACTH and KCl were decreased in the tumour rats at 14 days. Moderate hypercalcaemia (day 7 and 11), induced by Leydig cell transplantation in the Fischer rat, is associated, therefore with elevated blood pressure which appears to be related, in part, to activation of the reninangiotensin system. However, severe hypercalcaemia (day 14) was associated with hypotensive hyperreninaemic hypoaldosteronism state.
Vitamin E prolongs survival and function of porcine Leydig cells in culture
Authors: Mather J. P , Saez J. M. , Dray F. , Haour F.
Published: December 2008

Vitamin E (α-tocopherol) is known to be required for testicular function but its action on specific testicular cells has not yet been studied. The present study used procine Leydig cell cultures, in a hormone-supplemented medium, to study the effect of vitamin E (vit E) on Leydig cells. It was seen that the addition of vit E to the medium led to an increase in cell survival, lengthening the life span of the cultures from 3–4 days to more than a week. The Leydig cells maintained their LH/hCG receptors and responsiveness throughout this period as evidenced by an increase in testosterone (T) and prostaglandin secretion. The hCG stimulated T levels were synergistically increased in the presence of vitamin E, while basal levels of T secretion were not changed. Other secretory products of Leydig cells are prostaglandins E2 and F2α. It was found that the addition of vit E inhibited both the basal prostaglandin levels and the stimulated levels by 90%. Maximal effects on all of these parameters were seen at 10 ng/ml vit E. It is obvious that vit E plays a critical role in maintaining porcine Leydig cells in primary cultures beyond the first 3 days. This vitamin seems to be involved both in steroidogenesis and in prostaglandin production in the Leydig cells. The exact mechanism of the action of vit E these two biosynthetic pathways remains to be determined.
Impaired prolactin response to arginine infusion and insulin hypoglycaemia in chronic renal failure
Authors: Schmitz O. , Møller J.
Published: December 2008

The elevated level of circulating prolactin present in the majority of uraemic patients on chronic haemodialysis is primarily due to hypothalamic pituitary dysfunction. So far this defect has been illustrated by demonstration of a blunted prolactin response to TRH and failure of l-dopa to suppress prolactin levels. In the present study two powerful prolactin and growth hormone stimuli, namely iv arginine infusion and insulin hypoglycaemia were applied in a group of uraemic patients on chronic haemodialysis and in age matched control subjects. The prolactin increments to arginine infusion (4.4 ± 1.2 ng/ml vs 17.6 ± 4.6 ng/ml, mean ± se) and to insulin hypoglycaemia (7.9 ± 1.7 ng/ml vs 31.5 ± 5.4 ng/ml) were significantly suppressed in the uraemic patients compared to the controls (P < 0.05). In contradistinction the growth hormone rise provoked by the tests were similar in the two groups.

Our results provide further insight into the hypothalamic pituitary derangement in uraemic patients and confirm the presumption of an insensitivity of the lactotrophs to stimulation in uraemic patients.
Thyroid function in goitrous subjects with thyroxine binding globulin deficiency
Authors: Callan F. P. , Duffy M.J. , Duffy G.J. , Farrell R.J. , McKenna T.J.
Published: December 2008

The co-existence of thyroxine binding globulin (TBG) deficiency and euthyroid goitre in the same family raised the possibility that the disorders might be related. However, although both disorders co-existed in some members of the family, other members had either but not both conditions. These observations exclude the possibility that goitre development was solely due to alterations in thyroid activity brought about by TBG deficiency. It is possible, however, that the defect in protein binding might have enhanced goitre development in predisposed individuals as the two largest goitres occurred in TBG deficient subjects. Of the conventional parameters used to assess thyroid hormone levels in TBG deficient subjects, only the free triiodothyronine index consistently reflected the euthyroid status of these patients as established by clinical examination and TSH levels.
Recovery of thyroid function with a decreased titre of antimicrosomal antibody in a hypothyroid man with Hashimoto's thyroiditis
Authors: Yamamoto Makiko , Kaise Kazuro , Kitaoka Hirofumi , Yoshida Katsumi , Kaise Nobuko , Fukazawa Hiroshi , Sakurada Toshiro , Saito Shintaro , Yoshinaga Kaoru
Published: December 2008

A 36 year old man with a diffuse goitre, signs of mild hypothyroidism, strikingly low levels of T4 (0.9 μg/dl) and T3 (24 ng/dl), elevated TSH (140 μU/ml) and elevated microsomal haemagglutination antibody (MCHA, 1:409 600), subsequently became non-goitrous and euthyroid with a decreased titre of antimicrosomal antibody without any medication. At the time of surgical biopsy, serum levels of T4 and T3 had risen to the normal range (4.6 μg/dl and 73 ng/dl, respectively), serum TSH had decreased to 30 μU/ml and the titre of MCHA to 1:25 600. Thyroid specimens showed Hashimoto's thyroiditis. The activity of thyroid peroxidase (TPO) was normal. The latest examination, 1 year and 3 months after initial evaluation, showed that the patient remained euthyroid with no goitre, that serum thyroid hormones were within the normal range (T4 7.7 μg/dl and T3 97 ng/dl), and that TSH was not detectable. The titre of MCHA decreased strikingly to 1:400.
HLA antigens in a family with both parents and several siblings affected by Graves' disease
Authors: Castañer M. Fernández , Potau M. Angel , Reus J. Cabrer , Ercilla M. G.
Published: December 2008

A family with autoimmune thyroid disease is described. Four members had Graves' disease and 3 had diffuse goitres. Both parents (second cousins) carry the HLA haplotype: HLA Aw24, Bw39(w6), Cw-, DR3, MT2. Only females with this haplotype show thyroid symptoms. These findings emphasize the involvement of HLA linked genes in susceptibility to Graves' disease.
The effect of hyperglucagonaemia on blood glucose concentrations and on insulin requirements during fasting in insulin dependent diabetes mellitus
Authors: Clarke W. L. , Melton T. W. , Bright G. M.
Published: December 2008

The effect of sustained hyperglucagonaemia on blood glucose concentrations and on insulin requirements was evaluated in 6 fasting insulin dependent diabetic subjects whose blood glucose concentrations were being controlled with a closed loop insulin infusion system. Subjects were iv infused initially with either saline or glucagon and subsequently with the other infusate. All determinations were performed following the period during which transient increases in glucagon stimulated glucose production have been reported to occur.

Plasma glucagon concentrations were significantly higher during the glucagon study period (491±65 vs 70±13 pg/ml ± sd, P<0.001) as were blood glucose concentrations(104 ± 2 vs 84 ± 7 mg/ml ± sd, P<0.001) and insulin requirements (3.5 to 36.5 vs 0 to 2.3 mU/kg/h, P<0.05). Sustained hyperglucagonaemia continues to have an effect on glucose homeostasis for at least 2 h following the initiation of a continuous infusion.
Glucose- and arginine-induced insulin and glucagon responses from the isolated perfused pancreas of the BB-Wistar diabetic rat. Evidence for selective impairment of glucose regulation
Authors: Grill V. , Herberg L.
Published: December 2008

To investigate whether preferential responsiveness of residual B-cells is a feature of a diabetic state we compared insulin-releasing effects of glucose and arginine in perfused pancreases from moderately diabetic BB-Wistar rats. BB-rats were hyperglycaemic and insulin-dependent but possessed some insulin reserves (6 per cent of pancreatic content of control Wistar rats). Glucose (27.7 mm) failed to release insulin from diabetic pancreases while, conversely, arginine (8 mm) evoked a several-fold increase in insulin secretion. Ratios between responses from diabetic and normal pancreases were 0.01 and 0.29, respectively, when glucose or arginine were used as stimuli. This difference was significant (P < 0.05, Wilcoxon test). Glucose furthermore failed to exert a time-dependent (= priming) effect on arginine induced insulin secretion in the diabetic animals. Also A-cell responsiveness to glucose (acute and priming effects) were lost in BB-rats. It is concluded that selective loss of glucose effects on B- and A-cell secretion are associated with the diabetic state of the BB-Wistar rats.
Enhancement of corticosterone release by repeated injections of ACTH in the dexamethasone pre-treated rat
Authors: Murakami Noboru , Takahashi Kiyohisa
Published: December 2008

To examine the possibility that pulsatile secretion of adrenocorticotrophic hormone (ACTH) enhances the responsiveness of the adrenal, the blood corticosterone response to repeated injections of ACTH was determined in the dexamethasone-nembutal pre-treated rat. Treatment with dexamethasone (100 μg/100 g body weight) at 13.00 h for 2 days decreased corticosterone levels and completely abolished these daily variations in both the blood and adrenal. Under these conditions, four or five successive iv injections of 0.2 or 2 mIU ACTH were given at ½ or 1 h intervals. Blood samples were taken immediately before and at frequent intervals after injection. A significant increase of blood corticosterone levels was observed 10 min after the second injection of 0.2 mIU ACTH. Further increases in blood corticosterone levels were observed after the subsequent injections. In addition, repeated injections of 2 mIU ACTH augmented the responsiveness of the adrenal to ACTH. The second or the third injections of 2 mIU ACTH produced a greater increase in adrenal corticosterone content than did the first ACTH injection.

These results suggest that when ACTH acts on the adrenal gland in a pulsatile fashion, the steroidogenic response of the adrenal to ACTH increases markedly.
Induction of puberty by prolonged pulsatile LRH administration
Authors: Delemarre-van de Waal Henriette A. , Schoemaker J.
Published: December 2008

Pubertal maturation was induced in a 17.7 year old hypogonadotrophic boy by pulsatile LRH treatment. LRH was administered in three periods. During period one 20 μg LRH pulses were given iv 16 times per day for 10 weeks; during period two 2 μg LRH pulses iv 16 times per day for 12 weeks. During period three 2 μg LRH pulses 16 times per day were given sc for 13 weeks. Treatment was interrupted for 6 weeks between period one and two.

Rapid initiation of pubertal maturation was evidenced by an increase of penile length and testicular volume as well as by growth of pubic hair. After 21 weeks of treatment spermatozoa were observed in the ejaculate. Gonadotrophin levels increased from prepubertal values into the supranormal range in the beginning of period one, spontaneously declining to normal adult levels. A rapid increment of testicular volume during period one was also evidence for overstimulation.

During period two gonadotrophin levels were in the normal range.

Testosterone levels were normal during period one and two albeit higher during period one. We conclude that 1) pulsatile LRH treatment with 2 μg per pulse iv 16 times per day is an adequate and feasible way to induce puberty in hypogonadotrophic males with an intact pituitary. 2) Under pulsatile LRH treatment spermatogenesis takes place more rapidly than during normal puberty. 3) Testicular hormones exert a negative feedback action at the pituitary in the LRH treated hypogonadotrophic male. 4) The supranormal levels of LH and FSH during the first weeks of treatment may be caused by a delayed reaction of the testicles to gonadotrophin stimulation rather than to an overdose of LRH. 5) No evidence was found of a direct inhibitory action of LRH on testicular function.
Reversible inhibition of sperm production and gonadotrophin secretion in men following combined oral medroxyprogesterone acetate and percutaneous testosterone treatment
Authors: Soufir Jean-Claude , Jouannet Pierre , Marson Jocelyne , Soumah Arlette
Published: December 2008

Six men requesting male contraception received a daily oral dose of 20 mg medroxyprogesterone acetate (MPA) in combination with 50 or 100 mg percutaneous testosterone for 1 year. From the third month the sperm concentration was < 106/ml for all the men at one time or another during treatment, and usually < 5 × 106/ml, with an average reduction of 95% with respect to pre-treatment values. The sperm count returned to previous values 3–6 months after cessation of the treatment. While FSH and LH secretion was inhibited throughout the treatment period, plasma testosterone levels were not reduced. Oestradiol levels were unaffected while dihydrotestosterone was elevated. The secretory activity of the prostate and seminal vesicles was not appreciably affected; seminal carnitine concentration was reduced during the treatment with a subsequent return to pretreatment values. No pregnancies occurred during treatment. There was no impairment of libido in the subjects, nor any incidence of gynaecomastia, or increase in average body weight. The only observed metabolic side-effect was a moderate increase in glycaemia. A synergistic action of MPA and testosterone is proposed to explain the inhibition of gonadotrophin secretion.
Inhibition of the TSH secretion by histamine in male rats
Authors: Tuominen R. K. , Mattila J. , Männistö P. T.
Published: December 2008

Abstract. The effect of histamine (HA) on the coldstimulated and the TRH-induced TSH secretion was studied in male rats utilizing HA and specific HA antagonists and histaminergic drugs as tools. l-histidine (1000 and 1500 mg/kg ip) inhibited the cold-stimulated but not the TRH-induced TSH secretion. Mepyramine (5–50 mg/kg ip) and cimetidine (50–250 mg/kg ip) had no effect on the TSH-cold-response, but the TRH-induced TSH secretion was enhanced by them. HA (1 mg/kg sc), 2-pyridylethylamine (2PEA; 10 mg/kg ip) and impromidine (1 mg/kg sc) decreased the TRH-induced TSH secretion but did not affect the TSH cold-response. When infused into the third ventricle HA (1–50 μg/rat), impromidine (0.1 and 1.0 μg/rat) and 2PEA (50 μg/rat) decreased the cold-stimulated TSH-secretion. The locus of the inhibitory action of HA seems to be both at the anterior pituitary, where it is mediated through H1- and H2-receptors and in the hypothalamus, where the effect appears to be mediated through H2-receptors. At least a part of this particular action might be explained by other mechanisms since neither H1- nor H2-receptor antagonists were able to counteract the effect of HA.
Urinary free corticoids: an evaluation of their usefulness in the diagnosis of Cushing's syndrome
Authors: Trecan G. Vidal , Laudat M. H. , Thomopoulos P. , Luton J. P. , Bricaire H.
Published: December 2008

Abstract. We evaluated the usefulness of measurement of urinary free corticoids (UFC) in the diagnosis of hypercorticism. One hundred and thirty patients with features suggestive of Cushing's syndrome were examined. Twenty-six patients were proved to have Cushing's syndrome. The remaining 104 patients were considered not to have this disease on the basis of other investigations, and were designated as 'suspected patients'. UFC and 17-hydroxycorticosteroids were measured in all these patients in the basal state and on the 5th day of a low-dose-dexamethasone suppression test (3 mg/day for 5 days). UFC values of patients with Cushing's syndrome were well above 125 μg/24 h in the basal state and higher than 10 μg/24 h during the suppression test. UFC values of 'suspected patients' were between 20 and 125 μg/24 h in the basal state and below 10 μg/24 h during the suppression test.

It can be concluded that the measurement of UFC in the basal state and on the 5th day of a suppression test is not only a very sensitive but also a specific method for the diagnosis of Cushing's syndrome.
The endocrine control of the initiation and growth of antlers in white-tailed deer
Authors: Brown Robert D. , Chao Chun Chin , Faulkner Lewis W.
Published: December 2008

Abstract. Five fawn and 5 adult white-tailed deer (Odocoileus virginianus) were maintained in individual pens, fed a complete diet, and bled bi-weekly for one year. Blood serum was analyzed for testosterone (T), androstenedione (A), thyroxine (T4), calcium (Ca), phosphorus (P) and alkaline phsophatase (AP). Adults grew velvet antlers from mid-April and shed their velvet in mid-September. Hardened antlers were cast in March. Fawns grew velvet antler buttons which hardened in February and cast in March, prior to the growth of the first antlers. Adults had higher (P < 0.05) titres of T and A over the year. Fawns had higher T4 levels and AP activity (P < 0.05), while Ca and P levels were not different between the groups (P > 0.05). In the adults, T peaked in December and April and was correlated with the periods of hard antlers and the initiation of antler growth. In the fawns, T peaked in November and April and was correlated with hardened buttons and the initiation of the first antlers. Adult A peaked in June but hit nadirs in May and July and generally was not correlated with the antler cycle. In the fawns, A was similar to the T cycle. Thyroxine was relatively constant over the year in adults, but was elevated in the winter in fawns during the period of hardened buttons. Calcium and P levels were relatively constant throughout the year in both groups. AP activity was elevated over winter in adults and then decreased sharply when antlers were cast. Activity increased gradually again as new antlers grew. AP activity in fawns was elevated over the winter and spring and gradually declined as the first antlers developed.
Comparison of oestrogen and GnRH agonist analogue-induced inhibition of the pituitary-testicular function in rat
Authors: Huhtaniemi Ilop T. , Warren Dwight D. , Catt Kevin J.
Published: December 2008

Abstract. The purpose of the present study was to compare the inhibitory effects of oestrogen and a gonadotrophin releasing hormone agonist analogue (GnRH-A) on the pituitary-testicular function of adult rats. Animals were treated with sc injections of oestrogen (diethylstilboestrol, DES, 5 or 50 μg/kg body weight/day) or a gonadotrophin releasing hormone agonist analogue. [(D-Ser-(tBu)6)des-Gly10-GnRH N-ethylamide, GnRH-A, 0.4 or 4 μg/kg/day] up to 12 days. Serum LH (24 h after the last hormone injection) decreased by 83% in 3 days with DES, but was unchanged during 12 days of GnRH-A treatment. Serum testosterone (T) decreased by 98% during DES treatment, and also clearly but less profoundly, by 89%, with GnRH-A. Maximal decrease in the weights of the ventral prostate and seminal vesicles were 73–78% with DES-treatment, but clearly slower, and to a lesser extent, with GnRH-A (33–41%). Testicular weights decreased consistently (up to 41%) with GnRH-A treatment only. DES decreased the content of testicular LH receptors by 40% in 12 days whereas GnRH-A caused a loss of 97% in LH binding. Testicular lactogen receptors decreased to similar extents (by 68–78%) with both treatments. A clear increase in serum progesterone/T ratio was observed with both types of treatment, suggesting blockade of steroidogenesis at the C21 steroid level. These findings suggest that the antigonadal actions of oestrogen in the intact animal are largely due to a decrease of circulating gonadotrophin levels, and that those of GnRH-A are predominately due to Leydig cell LH-receptor down-regulation and steroidogenic lesions, induced by transiently elevated gonadotrophin levels. The inhibitory effects of oestrogen on testicular function appeared to be faster and more complete that those of GnRH-A in the present short-term experiments.
Dyslipoproteinaemia in hypothyroidism of pituitary origin: effects of l-thyroxine substitution on lipoprotein lipase, hepatic lipase, and on plasma lipoproteins
Authors: Valdemarsson Stig , Hedner Pavo , Nilsson-Ehle Peter
Published: December 2008

Abstract. We have studied the effects of l-thyroxine substitution on lipoprotein concentrations, on the activities of lipoprotein lipase (LPL) and hepatic lipase (HL), and on the elimination rate of exogenous triglyceride in a homogeneous group of patients with hypothyroidism of pituitary origin. All were deficient of sex hormones but not of corticosteroids during the observation period.

Before treatment total plasma cholesterol, LDL cholesterol, and triglyceride levels were significantly higher than in a euthyroid control group but not as high as in patients with overt primary hypothyroidism. The activities of LPL and HL were also intermediate between those of euthyroid and overt primary hypothyroid subjects, and there was a significant reduction of the elimination rate of exogenous triglyceride. No changes were found for HDL cholesterol levels.

When the patients with secondary hypothyroidism were compared to patients with primary hypothyroidism, matched for thyroid function levels, age, sex, and weight, there were no differences with regard to plasma lipoprotein concentrations or post-heparin lipase activities.

In 3 patients with secondary hypothyroidism the lipoprotein profiles were studied by zonal ultracentrifugation and found to agree well with changes observed in primary hypothyroidism.

l-thyroxine substitution produced a normalization of lipase activities and lipoprotein concentrations in patients with secondary hypothyroidism. We conclude that there are no fundamental differences in the disturbances of the lipoprotein metabolism in primary and secondary forms of hypothyroidism.
Immunohistochemical localization of thyroxine (T4) and triiodothyronine (T3) in the rat thyroid gland under various experimental conditions
Authors: Kawaoi Akira , Okano Tadao , Nemoto Norimichi , Shikata Toshio
Published: December 2008

Abstract. Detection of T4 and T3 in paraffin sections of the rat thyroid gland in various functional states was attempted by an immunoenzyme technique. Both hormones showed a similar localization, being detected mainly in the colloid in the follicular lumen, and sometimes in certain regions of the cytoplasm of the follicular epithelium. Following administration of TSH, their stainability was increased, and the localization within the cytoplasm became more remarkable. Decrease or disappearance of stainability was observed after hypophysectomy or administration of PTU.

These findings support the view that the immunostainability of T4 and T3 is closely correlated with the functional state of the thyroid gland.
Decrease in serum testosterone concentration during treatment with tetracycline
Authors: Pulkkinen M. O. , Mäenpää J.
Published: December 2008

Abstract. Serum concentrations of testosterone and the binding capacity of sex hormone binding globulin (SHBG) were measured on 2 days immediately preceding tetracycline treatment, on 3 days of treatment and on 2 days immediately after cessation of treatment. On the treatment days serum mean testosterone concentrations were significantly lower than on the control days (17 ± 0.9 vs 21 ± 0.8 nmol/l, P < 0.01). There were no differences in the SHBG. The 'free testosterone index' behaved like the total testosterone.
Concentrations of 2-methoxyoestrogens in human serum measured by a heterologous immunoassay with an 125I-labelled ligand
Authors: Berg D. , Sonsalla R. , Kuss E.
Published: December 2008

Abstract1. A radioimmunoassay has been developed for the measurement of 2-methoxyoestrogens in samples of human serum without chromatography after solvent extraction. Antibodies raised against 2-methoxyoestradiol-17β-hemi-succinyl-BSA served as binding protein and 2-methoxyoestrone-17-cmo-[125I]iodohistamine served as 125I-labelled ligand. A specific (little or no cross-reactivities to other oestrogens), sensitive (2.4 ± 0.9 pg/tube) and precise (6.5% intra-assay; 9.1% inter-assay) assay was obtained by employing this heterologous bridge system.
Primary hyperparathyroidism associated with primary hyperaldosteronism
Authors: Ferriss J. B. , Brown J. J. , Cumming A. M. M. , Fraser R. , Lever A. F. , Peacock M. , Robertson J. I. S.
Published: December 2008

Abstract. Two patients with both primary hyperparathyroidism and primary hyperaldosteronism are described. Each presented with high blood pressure and a history of renal calculi. Mild hypercalcaemia was associated with raised plasma parathyroid hormone concentrations and a parathyroid adenoma was excised from each. Both patients also had hypokalaemia, hyperaldosteronism and low plasma renin concentrations. Quadric analysis, adrenal vein plasma aldosterone concentrations, adrenal venography and CT scanning all suggested an adrenal adenoma in each patient. This suspicion was confirmed at operation in one patient; the other patient is unfit for adrenal surgery but her blood pressure and plasma potassium concentration have remained within the normal range during prolonged treatment with either spironolactone or amiloride.

Because of this unusual association a search was made for parathyroid hormone excess in patients with primary hyperaldosteronism and for aldosterone excess in primary hyperparathyroidism. None was found.
Effects of naloxone on the insulin and GH responses to α-adrenergic stimulation with clonidine
Authors: Massara F. , Limone P. , Cagliero E. , Tagliabue M. , Isaia G. C. , Molinatti G. M.
Published: December 2008

Abstract. To find if endorphins can influence hormonal responses mediated by noradrenergic pathways, we examined the effects of naloxone, an opiate receptor blocker, on the GH and insulin responses to clonidine, a drug which acts by stimulation of α-adrenergic receptors. Intravenous clonidine (0.15 mg in 10 min) induced a significant fall of plasma insulin and a marked increase of plasma GH.

Intravenous naloxone (bolus of 1.6 mg followed by 50 μg/min) did not change the insulin response to clonidine, and seemed to induce only a slight delay in the GH response.
Internalization of receptor-bound human chorionic gonadotrophin in preovulatory rat granulosa cells in vivo
Authors: Jääkeläinen Kalle , Markkanen Seppo , Rajaniemi Hannu
Published: December 2008

Abstract. The subcellular distribution of 125I-labelled human chorionic gonadotrophin (hCG) in preovulatory rat granulosa cells was studied in vivo. Pregnant mare serum gonadotrophin-pretreated immature female rats received an iv injection of [125I]hCG a few hours before the endogenous preovulatory gonadotrophin surge. The animals were killed at 2 or 6 h after the [125I]hCG injections. Light microscope autoradiographs showed that the mural granulosa cells of large follicles were the most highly labelled cells in the ovaries. Electron microscope autoradiography was used to study the subcellular distribution of radioactivity in the mural granulosa cells. At 2 h 45% of the counted silver grains were associated with the plasma membrane and 10% with the lysosomes, at 6 h the values were 51% and 9%, respectively. The distribution of the observed silver grains was compared with the generated expected source to grain pairs by computerized linear multiple regression analysis. The magnitudes of the regression coefficients revealed that the plasma membrane and the lysosomes were the only specifically 125I-labelled organelles, that a few radioactive molecules were located diffusely over the cytoplasm at 2 h and that the 125I-radioactivity of the nuclei was negligible. The present results suggest that preovulatory rat granulosa cells are in vivo able to internalize into lysosomes [125I]hCG initially bound to LH/hCG receptors of the plasma membrane.
Prenatal testosterone propionate and postnatal ovarian activity in the rat
Authors: Slob A. Koos , den Hamer R. , Woutersen P. J. A. , van der Werff ten Bosch J. J.
Published: December 2008

Abstract. Testosterone propionate (TP) was given to rats on days 16 through 20 of pregnancy (2 mg/day). Female young had masculinized external genitalia. Sexual maturity was accelerated in TP females, despite lower weights and shorter lengths of body and tail. Placental and body weights were lower in TP females and males than in controls. The inhibiting effect of TP on postnatal growth is probably mediated by its effect on birth weight through placental damage. Ovarian cyclicity occurred upon reaching sexual maturity. In one experiment TP females were ovariectomized at 6 weeks, and given ovarian and vaginal grafts. Most of these animals showed regular cyclicity in vaginal smears between 74–100 days. Thus neither the 'early', nor the 'delayed early androgen syndrome' occurred in these experiments.

This absence of effect of prenatal TP on ovarian cyclicity is attributable to a placental barrier for testosterone. When maternal plasma testosterone was raised 20-fold by exogenous TP, foetal testosterone levels remained unchanged. More detailed information was obtained when labelled testosterone was infused into a pregnant rat. Testosterone did not reach the foetus as such, but mainly as androsterone, which cannot be converted into oestrogens. This explains why prenatal TP can cause masculinization of genitalia, without 'masculinizing' the gonadotrophin secretion pattern in female rats. The latter process would presumably require oestrogenic compounds.
Effects of trifluoperazine on rat prolactin, growth hormone, thyroid stimulating hormone and adrenocorticotrophin secretion in vitro
Authors: Powell Ruth C. , Daniels Mark , Innes Graham K. , Ashby Michael J. , Mashiter Keith
Published: December 2008

Abstract. We have studied the effects of trifluoperazine, a proposed inhibitor of calmodulin directed cellular function, on adrenocorticotrophic hormone (ACTH), thyroid stimulating hormone (TSH), prolactin (Prl) and growth hormone (GH) secretion from primary cultures of rat adenohypophyseal cells. 5 × 10−6 m and 10−5 m trifluoperazine caused a significant (P < 0.005) reversible dose-related decrease in basal Prl secretion but was less effective on basal GH secretion, significant reversible inhibition (P< 0.005) occurring only with 10−5 m. Trifluoperazine did not consistently alter basal ACTH or TSH secretion but did inhibit 10−2 m theophylline stimulation of ACTH, Prl and GH secretion and 1.5 × 10−7 m TRH stimulation of TSH and Prl secretion. Paradoxically 10−5 m trifluoperazine enhanced theophylline stimulation of TSH secretion.

Our results show trifluoperazine to have differential effects on Prl, GH, ACTH and TSH secretion, which are consistent with the known calcium dependence of pituitary hormone secretion and may suggest a role for calmodulin in this process.
Effects of iodotyrosine deiodinase inhibition on serum concentrations and turnover of diiodotyrosine (DIT) and thyroxine (T4) in the rat
Authors: Meinhold Harald , Buchholz Reinhard
Published: December 2008

Abstract. Serum concentrations and metabolic clearance rates (MCR) of diiodotyrosine (DIT) and thyroxine (T4) have been measured by radioimmunoassay and tracer kinetic technique in both normal rats and rats treated with 3-nitro-l-tyrosine (MNT), a potent inhibitor of iodotyrosine deiodinase. In normal rats, DIT serum levels were 0.27 ± 0.12 nmol/l (mean ± sd); MCR was 15.9 ml/h 100 · g body weight (bw), and the turnover rate was 4.3 pmol/h · 100 g bw. Inhibition of iodotyrosine deiodination by treatment with 50 μmol MNT per day for 1 week caused a highly significant elevation of DIT serum levels to 4.80 ± 3.30 nmol/l, a decrease of MCR to 9.0 ml/h · 100 g bw and a ten-fold increase of the DIT turnover rate to 43.2 pmol/h · 100 g bw. Serum concentrations of T4 and T3 decreased slightly, whereas the T4 turnover rate (37.5 vs 37.8 pmol/h · 100 g bw) and rT3 serum levels remained unchanged under MNT treatment.

The study demonstrates the presence of measurable DIT serum concentrations in the normal rat. Inhibition of intra- and extrathyroidal iodotyrosine deiodinase leads to a situation in which circulating iodotyrosines play an equally important role in peripheral iodine turnover as the iodothyronines. Since DIT serum levels in normal and enzyme-blocked rats were comparable to those in normal human subjects and patients with iodotyrosine deiodinase defect respectively, MNT-treated rats afford a suitable experimental model for this disease.
PTH and vitamin D responses during treatment of hypomagnesaemic hypoparathyroidism
Authors: Ralston S. , Boyle I. T. , Cowan R. A. , Crean G. P. , Jenkins A. , Thomson W. S.
Published: December 2008

Abstract. The response of calcium regulating hormones in a patient with hypomagnesaemic hypoparathyroidism was assessed during magnesium infusion. Magnesium repletion was accompanied by prompt restoration of PTH secretion which subsequently stimulated 1,25-diOHD3 production, thus correcting hypocalcaemia. Further, failure of the patient to respond to previous 1α-OHD3 therapy suggests that severe magnesium depletion may also result in a state of acquired resistance to the active metabolites of vitamin D.
Immunohistochemical demonstration of salivary proline rich peptide P-C like immunoreactivity in human pancreatic B-cells
Authors: Ito Seiki , Isemura Satoko , Saitoh Eiichi , Sanada Kazuo , Suzuki Toshimitsu , Shibata Akira
Published: December 2008

Abstract. Antisera against proline rich peptide P-C, recently isolated from human whole saliva were raised in rabbits by injections of peptide P-C-BSA conjugates. Immunohistochemical study using the antisera was carried out on human salivary glands, gut and pancreas. The results showed that peptide P-C like immunoreactivity was present not only in the salivary glands but also in the pancreatic islets, though not in the gut. Furthermore, immunostaining of adjacent thin sections revealed that cells reacting with antisera against peptide P-C were identical to those reacting with insulin antisera. As the antisera against peptide P-C did not have any cross-reactivities to insulin, glucagon, somatostatin, pancreatic polypeptide, VIP and human C-peptide, the antisera were considered to recognize specifically either peptide P-C related antigen or peptide P-C itself in human pancreatic B-cells. A novel substance, peptide P-C like immunoreactivity, may be present in pancreatic B-cells independent of pro-insulin and insulin.

Morphological similarity between the salivary glands and the pancreas has been reported, and amylase, kallikrein and glucagon are present in both. These findings seem to suggest some functional relation between the pancreas and salivary glands. Detection of peptide P-C like immunoreactivity in the pancreas and salivary glands would be a additional support for this idea. Although it is suggested that peptide P-C like immunoreactivity in pancreatic B-cells may play some role in the function of B-cells, its exact pathophysiological role remains obscure.
Hormonal effects of beta-receptor blockade during exercise
Authors: Johansson G. , Uusitupa M. , Härkönen M. , Siitonen O. , Aro A. , Korhonen T.
Published: December 2008

Abstract. The effects of two different beta-receptor blocking agents, beta1-selective metoprolol (150 mg/day) and non-selective propranolol (120 mg/day), on hormonal responses to physical exercise (30 min bicycle ergometer test) were compared with placebo within a double-blind, cross-over design in 7 healthy male volunteers.

Plasma prolactin levels decreased from the initial values during and after exercise during treatments with placebo and beta-receptor blocking agents, but they were constantly higher with the two beta-blocking agents than with placebo. Exercise did not affect plasma testosterone levels, but during propranolol they remained higher than during placebo and metoprolol. The plasma LH and FSH levels were not affected by exercise, nor were they significantly modified by beta-blockade.

The results of this study as well as those of previous studies indicate that beta-receptor blocking agents interfere with physiological endocrine functions and that the non-selective agents may have more distinct effects in this respect.
Effect of an enkephalin-analogue (FK 33-824) on glucose tolerance in man
Authors: Jeanrenaud X. , Maeder E. , Del Pozo E. , Felber J. P.
Published: December 2008

Abstract. The purpose of the present work was to study the effect of a methionine-enkephalin analogue (FK 33-824) on glucose tolerance in man. Groups of 5 to 8 normal subjects were given a 0.5 mg im injection of the drug or placebo just before a 100 g oral glucose load or a 0.5 g/kg iv glucose load. In the enkephalin analogue treated subjects, diminished insulin response to glucose was observed following the oral glucose load, with insulin values significantly lower than in the controls from time 10 to 90 min, but no corresponding change in the glucose curve. This effect was not observed when glucose was given iv in another group of 5 subjects in whom the significant blunting of the insulin response was accompanied by a significant decrease in glucose tolerance.

These observations demonstrate that in man, enkephalin produces a decrease in insulin secretion in response to both oral and iv glucose loads. The absence of any marked impairment in glucose tolerance in the oral test in spite of the decreased insulin response suggests that enkephalin might have an additional effect in delaying glucose absorption.
Insulin resistance in patients with polycystic ovaries: its relationship to body weight and androgen levels
Authors: Pasquali Renato , Casimirri Francesco , Venturoli Stefano , Paradisi Roberto , Mattioli Loretta , Melchionda Nazario , Labò Giuseppe
Published: December 2008

Abstract. Using a combined infusion of somatostatin, insulin and glucose, insulin resistance was assessed in vivo in two groups of females with polycystic ovaries (PCO), obese (OB-PCO) and normal weight (NO-PCO) and in two groups of matched (for age, sex and body mass index) controls (OB and NO). A steady state plasma glucose (SSPG) and insulin (SSPI) was attained after 90 min. OB-PCO and NO-PCO showed higher SSPG with respect to matched controls. The SSPG levels were related to body mass index (r = 0.69; P < 0.001). The SSPG values were significantly correlated with the fasting insulin levels (r = 0.47; P < 0.003). Gonadotrophin and steroid peripheral blood concentrations were also evaluated in the PCO females. A significant correlation was found between the SSPG values and the dehydroepiandrosterone sulphate levels (r = 0.46; P < 0.05) and between the fasting insulin levels and the androstenedione concentrations (r = 0.64; P <0.01). 0.01). Moreover, significant correlation coefficients were found between the glucose to insulin ratio and the A (r = −0.59; P < 0.01) and the DHEA-S (r = −0.50; P <0.05) plasma levels. Finally, no relationship between body mass index and A or DHEA-s levels was found in PCO females considered as a group. We conclude that insulin resistance is present in females with PCO and it is mainly dut to the presence of obesity, but other factors such as androgen levels, probably of adrenal sources, must be considered as a cause.
Changes in bone metabolism during treatment of acromegaly
Authors: Bijlsma J. W.J. , Nortier J. W. R. , Duursma S. A. , Croughs R.J. M. , Bosch R. , Thijssen J. H. H.
Published: December 2008

Abstract. Bone metabolism was studied in 17 acromegalic patients, who responded to either medical treatment with bromocriptine (12 patients), or to transsphenoidal surgery (5 patients). Parameters of bone turnover decreased, e.g. serum acid phosphatase (9.2 ± 0.7 vs 8.1 ± 0.6 U/l, P < 0.05) and the ratio of hydroxyproline/creatinine (33.6 ± 4.4 vs 18.3 ± 2.0, P < 0.01) in the urine. No changes were observed in parathyroid function or concentrations of calcitonin. Serum 1,25-dihydroxycholecalciferol decreased (32.6 ± 3.6 vs 20.6 ± 1.8 ng/1, P < 0.01) and 24,25-dihydroxycholecalciferol increased (4.3 ± 0.6 vs 6.7 ± 1.0 μg/l, P < 0.05). No correlation between the percentual changes in serum growth hormone levels and 1,25-dihydroxycholecalciferol was found, suggesting an indirect effect of growth hormone on the renal 25-hydroxycholecalciferol-1-alpha-hydroxylase. The possible mechanisms involved are discussed, including the effects of growth hormone and somatomedin on bone.
Influence of dopaminergic inhibition on serum levels of thyrotrophin and prolactin in patients with hypothyroidism before and after prolonged oral administration of TRH
Authors: Frey Harald M. M. , Haug Egil
Published: December 2008

Abstract. Forty mg TRH/day given orally for 3 weeks to 8 patients with mild primary hypothyroidism decreased serum TSH from a mean of 4.0 ng/ml ± 1.2 (se) to 2.0 ng/ml ± 0.4 (49%), and their mean incremental TSH response to iv TRH was equally reduced from 8.6 ng/ml ± 2.5 to 4.0 ng/ml ± 1.9 (46%). In the same patients serum Prl was 8.2 ng/ml ± 2.2 before oral TRH treatment and 6.6 ng/ml ± 1.5 (81%) after treatment, and the mean incremetal Prl response to iv TRH was reduced from 43.5 ng/ml ± 5.0 to 35.9 ng/ml ± 7.5(83%).

The oral administration of 10 mg of the dopamine antagonist metoclopramide increased mean serum TSH from 0.6 ng/ml ± 0.1 (se) to 0.7 ng/ml ± 0.1 (120%) in euthyroid subjects and from 4.0 ng/ml ±1.2 to 5.7 ng/ml ± 1.6 (145%) in patients with primary hypothyroidism, and mean serum Prl from 8.6 ng/ml ± 0.8 to 109.5 ng/ml ± 24.3 (1251%) and from 8.2 ng/ml ± 2.2 to 119.6 ng/ml ± 45.5(1460%), respectively.

The incremental TSH responses to iv TRH increased 2.3-fold in euthyroid subjects pre-treated with metoclopramide, while no change was observed in the TSH responsiveness in patients with primary hypothyroidism following metoclopramide pre-treatment. In the euthyroid subjects metoclopramide treatment had no effect on the Prl response to iv TRH. In the primary hypothyroid group metoclopramide pre-treatment caused a reduced Prl response to iv TRH in more than 50% of the patients. It is concluded that long-term TRH treatment decreased the serum levels of TSH and Prl as well as the incremental increases in TSH and Prl to iv TRH stimulation in patients with primary hypothyroidism. Long-term TRH treatment did not change the TSH and Prl responses to the dopamine antagonist metoclopramide.