bluuebunny/crossref_metadata_2025 huggingface dataset:
Prolactin in hirsute women: possible roles for androgens in suppressing basal levels, and for oestrogens in enhancing TRH-induced responses
Authors: McKenna T. Joseph , Cunningham Sean , Culliton Marie , Daly Leslie , Moore Aideen , Magee Fergal , Smyth Peter P. A.
Published: December 2008

Abstract. Hyperprolactinaemic patients occasionally demonstrate hirsutism and elevated levels of DHA-S, a weak androgen of adrenal origin. Abnormal adrenal function is frequently observed in hirsute patients. These observations prompted speculation that prolactin may modulate normal adrenal secretion and that derangements of adrenal androgen secretion may be due to abnormalities in prolactin. In this study we examined the possibility that elevated prolactin levels may be involved in the pathogenesis of hyperandrogenaemia in hirsute patients. However, basal prolactin levels in hirsute women, with or without menstrual disturbances, 201 ± 24.3 mU/l (mean ± se) and 192 ± 24.3 mU/l respectively, were significantly suppressed below levels in normal women, 289 ± 12.2 mU/l. The prolactin responses to stimulation with TRH and to suppression with l-dopa were also studied in hirsute patients. The prolactin response to TRH (maximum increment or integrated response) was exaggerated significantly in hirsute women with menstrual disturbances when compared to normal women, to hirsute women with normal menses or to normal men. This abnormal response may have been due to elevated oestrone levels present in patients with oligomenorrhoea (318 ± 49.5 pmol/l compared to 191 ± 12.1 pmol/l in normal women and 161 ± 15.5 pmol/l in hirsute women with normal menses, P < 0.05). There were no abnormalities detected in the suppression of prolactin in response to l-dopa in any of these groups. These findings do not support a role for prolactin in the pathogenesis of hyperandrogenaemia in hirsute patients. However, elevated androgen levels in women may bring about suppression of basal prolactin levels to values seen in normal men. In addition elevated oestrone levels may exaggerate the stimulatory effect of TRH on prolactin secretion. as was seen in oligomenorrhoeic hirsute women.
The combination of insulin and sulphonylurea in the treatment of secondary drug failure in patients with type II diabetes
Authors: Groop Leif , Harno Kari , Tolppanen Esa-Matti
Published: December 2008

Abstract. Thirteen patients (6 females and 7 males) who were secondary failures on oral drug therapy were randomly allocated to either 2 months of treatment with insulin + glibenclamide or insulin + placebo. Thereafter the treatment schedules of the two groups were switched over for another two months.

The combination of insulin and glibenclamide was more effective in lowering the fasting blood glucose (P = 0.026) and 24 h urine glucose (P = 0.042) than the combination of insulin and placebo. The combination therapy with insulin and glibenclamide revealed higher basal (P = 0.021) and glucagon-stimulated C-peptide concentrations (P = 0.037) than therapy with insulin and placebo. However, insulin binding to erythrocytes did not differ between the two study periods. The results indicate that the addition of glibenclamide to insulin in type II diabetics poorly controlled by oral antidiabetics alone may slightly improve diabetic control. The mechanism of this action is due at least partly to sulphonylureainduced stimulation of endogenous insulin secretion.

The effectiveness of the combination treatment during long-term therapy still remains to be proven, however.
Prolactin and the control of cycle length in the female rat
Authors: Boehm N. , Plas-Roser S. , Aron Cl.
Published: December 2008

Abstract. Bromocriptine (BRC) was injected on oestrus afternoon at 16.00 h into 5-day cyclic female rats thus causing reduced cycle length to 4-days. When injected on dioestrus 1 at 13.00 h the drug remained without effects. Blood progesterone concentration on dioestrus 1 afternoon and on dioestrus 2 morning was shown to be lower in 5-day cyclic rats given BRC than in their untreated counterparts. No changes in the rate of follicular growth were observed on dioestrus 2 afternoon in BRC injected 5-day cyclic rats. The pattern of prolactin secretion on oestrus afternoon was compared in 4- and 5-day cyclic female rats. High prolactin values were observed on early afternoon in the former and on late afternoon in the latter. The decline in progesterone secretion during the dioestrous period of the cycle was supposed to be responsible for cycle shortening in 5-day cyclic rats given BRC. It was concluded that prolactin might play a critical role in the establishment of a 5-day rhythm in the rat by controlling progesterone secretion during the dioestrous period of the cycle.
Urinary and nephrogenous cyclic AMP and renal phosphate handling in normal subjects and patients with parathyroid dysfunction
Authors: Khoury S. , Tucci J. R.
Published: December 2008

Abstract. Studies were performed in 60 patients with proven primary hyperparathyroidism pre-operatively and in 54 of these patients post-operatively, 22 patients with permanent hypoparathyroidism and 34 normal subjects. Urinary and nephrogenous cyclic AMP excretion were increased in the hyperparathyroid patients with an overlap of values with the normal group of 10 and 9%, respectively. Values fell in all patients post-operatively, and were decreased in those with permanent hypoparathyroidism. TmPO4/GFR was decreased in the preoperative hyperparathyroid patients and rose postoperatively while it was increased in the hypoparathyroid patients with an overlap of values with the normal group of 9%. Post-operative hypocalcaemia due to bone hunger was associated with continuing normo- or hypophosphataemia and urinary cyclic AMP that exceeded 4.5 nm/dl GF while those who developed permanent hypoparathyroidism had hyperphosphataemia, increased TmPO4/GFR and urinary cyclic AMP that was less than 3.5 nM/dl G.F. Urinary and nephrogenous cyclic AMP were equally effective in characterizing patients with primary hyperparathyroidism and less effective in distinguishing patients with hypoparathyroidism from normal while TmPO4/GFR estimates were more effective in delineating the hypoparathyroid state.
Kinetics of 5-hydroxytryptophan potentiation of glucose-induced insulin release
Authors: Lindström Per
Published: December 2008

Abstract. We have previously shown that l-5-hydroxytryptophan (l-5-HTP) potentiates glucose-induced insulin release in islets isolated from ob/ob-mice. In the present study, the kinetics of this effect were further studied. The combined effect of glucose and l-5-HTP was dependent on the concentration of both compounds. The threshold concentration for the potentiating effect of 5-HTP was on the order of 0.01–0.1 mmol/l, and the maximal effect was reached at 1–4 mmol/l extracellular concentration. l-5-HTP enhanced glucose-induced insulin release without changing the apparent Km for glucose (9.5–10 mmol/l). The effect of l-5-HTP increased with time for about 40 to 60 min and was reversibly reduced when either l-5-HTP was omitted or the glucose concentration was lowered. These findings support the view that l-5-HTP is a strong potentiator of glucose-induced insulin release.
Evidence for existence of somatostatin-like immunoreactivity with molecular heterogeneity in porcine ovaries
Authors: Mori Takahide , Saito Haruhiko , Ohno Yoshio , Irahara Minoru , Hosoi Eiji , Saito Shiro
Published: December 2008

Abstract. Measurement of somatostatin (SRIF) by RIA in porcine ovarian tissues after removal of the follicular fluid revealed the existence of immunoreactive (IR) SRIF at concentrations of 2.2 ± 0.6 ng/g wet weight (mean ± sd). On gel chromatographic analysis of ovarian extracts one major and two minor components with SRIF-like immunoreactivities have been detected. The major component comprised 59.5 ± 15.1% of the total IR-SRIF and was coeluted with synthetic tetradecapeptide (SRIF 14). The two other components seemed to have almost the same molecular weights as synthetic octacosapeptide (SRIF 28) (25.1 ± 10%) and pro-somatostatin (15.4 ± 5.5%), respectively. It is concluded that SRIF in porcine ovaries is heterogeneous, comprising SRIF 14 as a major component, as well as larger forms of SRIF which probably represent SRIF precursors.
Concentration of cyclic AMP in rabbit ovaries in the preovulatory period after administration of luteinizing hormone or human chorionic gonadotrophin
Authors: Patwardhan Vasant V. , Lanthier André
Published: December 2008

Abstract. Ovarian adenosine 3'-5'-monophosphate (cAMP) concentrations were determined in untreated female rabbits and in those sacrificed at various times (0.5–6.0 h) after administration of luteinizing hormone (LH, 50 μg) or human chorionic gonadotrophin (hCG, 100 IU). Both LH and hCG caused a rapid increase in ovarian cAMP concentrations within 0.5 h. After LH stimulation the elevated levels declined rapidly and by 2 h they were almost back to control levels. In the hCG-treated animals the decline in ovarian cAMP from the initial peak concentrations was much more gradual and the levels were significantly higher than control even at 6 h. The different response to the two gonadotrophins is discussed in relation to the physiologic importance earlier attributed to the prolonged elevation of cAMP in rabbit ovaries after stimulation with hCG.
Comparative therapeutic benefit of indomethacin, hydrochlorothiazide, and acetyl-salicylic acid in a patient with nephrogenic diabetes insipidus
Authors: Vierhapper H. , Jörg J. , Favre L. , Vallotton M. B. , Waldhäusl W.
Published: December 2008

Abstract. To define the importance of renal prostaglandins in nephrogenic diabetes insipidus (NDI), diuresis and the urinary excretion of PGE2 and PGF2α were studied in a patient with NDI before and during inhibition of endogenous prostaglandin synthesis with either indomethacin (IND) or acetyl-salicylic acid (ASA). The excretion rates of PGE2 and PGF2α were in the low normal range for the patient's age group, remained unchanged during 6 h of fluid deprivation and were suppressed by IND (150 mg/day), ASA (3 g/day), and by the combination of IND and hydrochlorothiazide (HCT, 50 mg/day). However, whereas IND, HCT, and the combination of IND and HCT reduced diuresis ASA did not. Free water clearance as determined during fluid deprivation remained positive during each phase of therapy. These data fail to demonstrate a direct effect of endogenous ADH on renal prostaglandin synthesis in NDI. The ineffectiveness of ASA to reduce diuresis indicates that indomethacin affects diuresis in NDI by a mechanism other than inhibition of cyclooxygenase.
The effects of dopaminergic blockade on serum TSH and prolactin levels in thyrotoxicosis
Authors: Swart S. , O'Malley B. P. , Vora J. , Barnett D. B. , Rosenthal F. D.
Published: December 2008

Abstract. In the first part of this study, we have demonstrated that, in 7 patients with untreated thyrotoxicosis, a 7 day regime of the long acting dopamine antagonist metoclopramide (10 mg orally 8 hourly) produces more adequate dopaminergic blockade at pituitary level than a single oral 10 mg dose of the compound as assessed by serum prolactin responses.

Subsequently, we have employed this protracted oral metoclopramide regime to evaluate the contribution of dopaminergic tone to the abnormal TSH and prolactin responsiveness of thyrotoxicosis. Serum TSH and prolactin responses to iv TRH (200 μg) were measured in 10 untreated thyrotoxic patients before and after a 7 day period of metoclopramide 10 mg orally 8 hourly. Ten euthyroid individuals were studied in similar fashion, their serum samples being analysed for prolactin levels alone, thus providing a control group for prolactin responsiveness to TRH, before and after metoclopramide.

In the thyrotoxic patients basal TSH levels did not change as a consequence of metoclopramide therapy and the TSH response to TRH remained flat. Basal prolactin levels were similar in thyrotoxic and euthyroid individuals and the increase in prolactin, seen in both groups after metoclopramide, was smaller in the thyrotoxic group than in the euthyroid group. Prolactin responsiveness to TRH was significantly impaired in the thyrotoxic subjects as compared to euthyroid subjects. After metoclopramide there was a significant decline in prolactin responsiveness in the euthyroid group, and a similar, though insignificant, trend in the thyrotoxic patients.

We conclude that in thyrotoxicosis dopaminergic tone plays no major part in the suppression of TSH levels, nor in the impaired prolactin responsiveness to TRH.
Insulin hypoglycaemia test guided by a glucose controlled insulin infusion system
Authors: Müller-Esch Gert , Ball Peter , Heidbüchel Karen , Wood William Graham , Scriba Peter C.
Published: December 2008

Abstract. Insulin hypoglycaemia test (IHT) for assessment of hypothalamic-pituitary-adrenocortical (HPA) function in patients with pituitary tumours is usually performed by bolus injection of insulin, a procedure which includes the risk of overdosage and/or the need of repeated administration. This study describes that a glucose controlled insulin infusion system (GCIIS) permits to perform the IHT with standardized hypoglycaemia. Ten healthy volunteers and 10 patients with pituitary tumours were studied using the GCIIS (Biostator®) on static control (Mode 1:1, BI 35, QI 10, RI 20, FI 300). Insulin administration was discontinued and the GCIIS used only for monitoring of blood glucose (BG), when BG had fallen below 40 mg/dl and initial clinical symptoms for hypoglycaemia were observed. In controls, the GCIIS guided IHT achieved a sufficient degree of hypoglycaemia (BG 27.6 ± 2.0 mg/dl; mean ± sem) and physiological responses for GH (peak 49.4 ± 6.7 ng/ml), Prl (peak 1766 ± 614 μU/ml), ACTH (peak 76.0 ± 8.7 pg/ml) and cortisol (peak 252 ± 15 ng/ml). The total amount of insulin given was 0.115 ± 0.012 U/kg. In the patients with pituitary tumours however, the required insulin dose varied markedly from 0.090 (pituitary insufficiency) to 0.340 U/kg (Cushing's syndrome). Minimum BG obtained was 32.5 ± 1.9 mg/dl. Partial impairment of hypothalamic-pituitary function and, in particular, patients requiring exogenous cortisol supplementation during stress, could be identified. In conclusion, special advantages of the GCIIS-guided IHT are:

Optimal insulin dosage with standardized hypoglycaemia due to automatic adjustment to the individual insulin sensitivity.

Patients' safety by earlier recognition of due insulin discontinuation as a result of continuous blood glucose analysis.
The effects of bradykinin on the contractile activity of the isolated rat ovary
Authors: Smith Caroline , Perks A. M.
Published: December 2008

Abstract. Studies of ovarian contractility were carried out on 43 rat ovaries maintained in vitro. Eighteen ovaries showed spontaneous motility. In 65 of 155 tests (42%), synthetic bradykinin (3.75–25.0 ng/ml saline) produced sustained increases in ovarian tone, or stimulated phasic contractions. Failure to respond was related to the stage of the oestrous cycle. Sensitivity was highest around ovulation (00.00–04.00 h oestrus), when there were 25 responses in 26 tests, and the linear relationship between the response and the logarithm of the concentration suggested a threshod of 2.9 ng/ml saline. Sensitivity fell later in oestrus, and reached its lowest point in metoestrus (1 reponse in 20 tests). Since the plasma kinin system is activated before ovulation, and the threshold to bradykinin was within reported plasma kinin levels, it seems possible that plasma kinins are involved in contractile processes associated with ovulation.
Inhibition of foetal growth hormone (GH) and thyrotrophin (TSH) secretion after maternal administration of somatostatin
Authors: Roti Elio , Robuschi Giuseppe , Alboni Alessandro , Emanuele Rossella , Amato Lorenzo d' , Gardini Eliana , Salvi Mario , Aglio Elisabetta Dall' , Gnudi Angelo , Braverman Lewis E.
Published: December 2008

Abstract. Somatostatin (SRIF) was infused (500 μg over 30 min) into 68 pregnant women during labour. As a control, saline was infused into 26 pregnant women. Maternal blood was obtained prior to the infusion and at delivery and cord blood was obtained at delivery. The subjects were divided into 4 groups based upon the interval of time from the termination of SRIF infusion and delivery. There was a marked decrease in cord blood thyrotrophin (TSH) from 0 to 180 min and in cord blood growth hormone (GH) from 0 to 120 min following SRIF infusion. SRIF infusion did not affect cord blood iodothyronine and thyroglobulin concentrations. SRIF administration induced a small but significant (P < 0.05) decrease in serum GH concentration but had no other effect on maternal hormone values. These studies strongly suggest that SRIF crosses the human placenta and transiently suppresses foetal anterior pituitary TSH and GH secretion.
Prl, TSH, FSH, β-hCG and oestriol responses to repetitive (triple) LRH/TRH administration in the third trimester of human pregnancy
Authors: Pérez-López F. R. , Robert J. , Teijeiro J.
Published: December 2008

Abstract. The effects of repetitive administration of 50 μg of LRH and 100 μg of TRH in a single bolus at 0, 90 and 180 min on Prl, TSH, FSH, μ-hCG and oestriol were tested in 11 healthy pregnant women in their third trimester of pregnancy. Basal hormonal levels were in agreement with previous reports. The Prl and TSH peaks after each injection of LRH/TRH were similar for each hormone. No significant changes in serum FSH, β-hCG and oestriol were detected after repetitive administration of LRH/TRH.

Thus, the responsiveness of lactotroph and thyrotroph cells to pulsatile stimulation with LRH/TRH is not altered during the last trimester of pregnancy, and FSH, β-hCG and oestriol levels remain constant during the period of sampling.
Foetal exposure to low doses of cyproterone acetate in the rat leads to functional endocrine abnormalities despite normal sexual morphogenesis
Authors: Gómez Fulgencio , Monnier Bernard , Lemarchand-Béraud Thérèse
Published: December 2008

Abstract. Cyproterone acetate (CPA), an anti-androgen and a gestagen, was administered to pregnant Wistar rats at very low doses (0.5 or 1.0 mg/day) between days 15 and 20 of pregnancy. No anatomical abnormalities were observed in external genitalia of their offspring, either immediately after birth or upon reaching maturity. However, when these animals were studied in adulthood, several endocrine abnormalities became apparent.

While the pituitary content of Prl decreased in the CPA-exposed offspring, the amount of LH increased. Plasma Prl was lower and FSH was higher in treated females whereas plasma LH was higher in both sexes compared to controls. Treatment induced a Prl-responsiveness to TRH in both sexes and an enhanced LH- and FSH-response to GnRH in females.

Testicular weights, LH/hCG receptors in testicular membrane preparations and testosterone response to in vivo hCG stimulation were identical in both the treated and control groups. Basal testosterone, however, was increased in the face of decreased ventral prostate weight and of decreased androgen receptors in prostate cytosol, indicating androgen resistance of the target organ.

Females displayed normal oestrous cycles, but possessed enlarged ovaries and uteri. The decrease in oestrogen receptors (ER) in uterine cytosol during oestrus and the relative increase of ER in dioestrus were consistent with enhanced oestrogenic action, presumably by increased oestrogen secretion by the hyperstimulated ovaries.
Identification of human semen insulin-like growth factor-I/somatomedin-C immunoreactivity and binding protein
Authors: Baxter Robert C. , Martin Janet L. , Handelsman David J.
Published: December 2008

Abstract. Human seminal plasma (SP) samples have been tested for insulin-like growth factor-I/somatomedin-C (IGF-I/SM-C) immunoreactivity. Gel chromatography of SP at neutral pH indicated that all immunoreactive IGF-I/SM-C was present at a higher molecular weight than the free peptide from plasma, while in 1 m acetic acid, a major peak of immunoreactivity was seen at an apparently lower molecular weight than the free peptide, together with a peak with molecular weight about 40000. This latter peak contained a binding protein which, on Scatchard analysis, was shown to have a single class of binding site, Ka = 1.2 × 1010 l/mol. The low molecular weight peak material was displaced from monoclonal and polyclonal IGF-I/SM-C antibodies parallel to standard preparations. Its elution on gel chromatography later than plasma IGF-I/SM-C was shown by re-chromatography to be due to physical retardation on the column, rather than a lower molecular weight. As acid-ethanol extraction of SP samples failed to remove binding activity, samples from patients were all subjected to acid gel chromatography before assay. The mean IGF-I/SM-C content in 5 normal men was 20.7 ± 3.7 (sd) ng/ml while that for 4 azoospermic subjects was 9.2 ± 3.7 ng/ml. A hyposomatotrophic subject with normal sperm density and low serum IGF-I/SM-C had an SP IGF-I/SM-C value in the normal range. This study indicates that human semen contains protein-bound immunoreactive IGF-I/SM-C which is at least in part of testicular origin, and apparently not growth hormone-dependent.
Variation with age in the levels of sex-steroid-binding plasma protein as determined by radioimmunoassay
Authors: Maruyama Yoshiyuki , Aoki Norihiko , Suzuki Yasuyuki , Sinohara Hyogo , Yamamoto Toshio
Published: December 2008

Abstract. A radioimmunoassay for human sex-steroidbinding plasma protein (SBP) was developed. With this assay, SBP was determined in sera of 138 normal men and 169 non-pregnant women, ranging in age from 11 to 87 years. The results indicate (i) that SBP levels in both sexes increase gradually with age up to mid-eighties, (ii) that the average levels in mid-eighties are approximately twice those in early twenties, and (iii) that the average levels in women are about twice as high as those in men of corresponding age. These results may also account for the discrepancies in the previous papers regarding the normal blood levels and sexual difference of SBP in adult men and women.
Familial hypocalciuric hypercalcaemia: evidence for continued enhanced renal tubular reabsorption of calcium following total parathyroidectomy
Authors: Davies M. , Adams P. H. , Lumb G. A. , Berry J. L. , Loveridge N.
Published: December 2008

Abstract. A patient with familial hypocalciuric hypercalcaemia (FHH) is reported. Seven years after total parathyroidectomy he remained hypocalcaemic, with biochemical evidence of hypoparathyroidism (enhanced renal tubular reabsorption of phosphate, low nephrogenic cyclic AMP excretion, and reduced serum concentration of 1,25-dihydroxycholecalciferol in the presence of normal renal function and normal serum 25-hydroxyvitamin D levels). Iv infusions of calcium were given before and 6 years after total parathyroidectomy. The renal tubular reabsorption of calcium was compared in these two situations. No difference was found. Before and after parathyroidectomy there was enhanced renal tubular reabsorption of calcium. It is concluded that the enhanced renal tubular reabsorption of calcium in FHH is independent of parathyroid hormone. Total parathyroidectomy corrects the hypercalcaemia in FHH by a reduction in the input of calcium into the extra-cellular fluid from gut and or bone perhaps as a result of reduced renal synthesis of 1,25-dihydroxycholecalciferol.
Immunohistochemical demonstration of relaxin in the placenta after removal of the corpus luteum
Authors: Yki-Järvinen H. , Wahlström T.
Published: December 2008

Abstract. We studied the occurrence of relaxin in the term placenta from a woman who had normal pregnancy after her corpus luteum had been removed at the beginning of the second trimester. Two antisera (antiserum R6 and anti-NIH-RXN-Pl. 3000 U mg) against highly purified porcine relaxin and the avidin-biotinylated antirabbit IgG method were used to detect relaxin-like immunoactivity. Specific staining for relaxin was seen in the placental syncytiotrophoblasts. Comparison to a placenta from a normal term delivery revealed no differences in the intesity or distribution of staining. Our case substantiates that the corpus luteum is not the only tissue producing relaxin during pregnancy.
Circulating vitamin D metabolites and hypercalcaemia of malignancy
Authors: Ralston Stuart H. , Cowan Robert A. , Robertson Andrew G. , Gardner Mary D. , Boyle Iain T.
Published: December 2008

Abstract. Plasma concentrations of 1.25 dihvdroxvcholecalciferol were measured in 44 patients with malignancy associated hvpercalcaemia and related to other hormonal regulators of calcium metabolism. Immunoreactive PTH concentrations were suppressed in all but 2 patients and, as a group, patients with hvpercalcaemia of malignancy had lower 1,25 dihydroxycholecalciferol concentrations than normocalcaemic cancer patients.

1,25 dihydroxycholecalciferol concentrations were clearly detectable in a significant proportion (43%) of hypercalcaemia cases however, suggesting that in these patients the active vitamin D metabolite may contribute to the pathogenesis and maintenance of the hypercalcaemia by stimulating bone resorption, and/or by increasing absorption of calcium from the intestine. Measurement of plasma 1,25 dihydroxycholecalciferol concentration does not provide a wholly reliable method for distinguishing the hypercalcaemia of malignancy from primary hyperparathyroidism.
Effect of growth hormone on osteoblasts and demonstration of somatomedin-C/IGF I in bone organ culture
Authors: Stracke H. , Schulz A. , Moeller D. , Rossol S. , Schatz H.
Published: December 2008

Abstract. Bone organ culture makes it possible to observe the direct influence of hormones on bone cells. We studied the effect of growth hormone in vitro on embryonal rat tibiae during culture for 7 days, functionally by measuring the levels of alkaline phosphatase in the culture medium, and morphologically by means of semithin sections and electron microscopic examination. Since growth hormone (GH) is supposed to exert an indirect effect on bone cells, somatomedin-C/insulin-like growth factor I (SM-C/IGF I) as a possible mediator was also measured radioimmunologically in the culture medium. In the controls alkaline phosphatase levels showed a continuous increase up to the 7th day which was significantly higher in the presence of GH. There was also a significantly enhanced increase of SM-C/IGF I in the presence of GH during culture in comparison to the controls. Evidently IGF I is produced locally in bone and mediates the effect of GH on bone formation.
Flunarizine, a calcium influx blocker, inhibits TRH- but not potassium-stimulated prolactin secretion
Authors: Merritt Janet E. , Tomlinson Stephen , Brown Barry L.
Published: December 2008

Abstract. The effect of flunarizine on the secretion of prolactin from monolayer cultures of normal rat pituitary cells has been determined. Both basal and TRHstimulated secretion were found to be significantly inhibited by micromolar concentrations of flunarizine, whereas depolarization (high K+)-stimulated secretion was virtually unaffected. These results indicate that TRH-stimulated prolactin secretion probably involves calcium influx and that flunarizine may be useful as a probe for particular Ca2+ channels.
Endocrine involvement in children with β-thalassaemia major. Transverse and longitudinal studies. I. Pituitary-thyroidal axis function and its correlation with serum ferritin levels
Authors: Cavallo L. , Licci D. , Acquafredda A. , Marranzini M. , Beccasio R. , Scardino M. L. , Altomare M. , Mastro F. , Sisto L. , Schettini F.
Published: December 2008

Abstract. Thyroid function was investigated by a TRH test in 24 clinically prepubertal children, 3–15 years old with β-thalassaemia major; in 7 of them the test was repeated once and in 2 twice at intervals of at least 12 months. Basal T4, T3, TBG and TSH levels and the TSH levels during a TRH test were determined and correlated with age and serum ferritin levels.

Basal serum T4, T3 and TBG levels were lower and serum TSH levels were higher during the test and in the basal state in thalassaemia major children than in control children.

These results show a compensated sub-clinical primary hypothyroidism.

The transversal study did not show any significant correlation between the hormonal parameters studied and chronological age or serum ferritin levels.

In contrast, the longitudinal study showed a significant correlation between pituitary-thyroidal axis function and siderosis (positive correlations between the variations of TSH levels as Δ, peak, 30 and 45 min values and the variations of serum ferritin levels).

The thyroid impairment seems not to be correlated with serum ferritin levels in the transversal study because of the presence of an individual different sensitivity of the gland to the iron overload. The ferritin dependence of this impairment is shown only by longitudinal studies where individual differences in sensitivity of the gland are absent.

Therefore iron chelation by desferrioxamine sc infusions, resulting in a decrease of ferritin, improves the deficient thyroid function.
Analysis of immunoreactive and biologically active human parathyroid hormone-peptides by high-performance-liquid-chromatography
Authors: Schettler T. , Kolk B. Aufm' , Atkinson M.J. , Radeke H. , Enters C. , Hesch R. D.
Published: December 2008

Abstract. A combination of high-performance-liquidchromatography (HPLC), sensitive radioimmunoassays and a homologous in vitro bioassay was used to characterise human parathyroid hormone (hPTH)-peptides in human parathyroid adenoma and plasma. Chromatography of several synthetic hPTH-peptides allows the calibration of the HPLC column. On the basis of sequence hydrophobicity the elution position of peptides can be predicted. A model for the determination of the minimal peptide sequence of each peptide has been developed which based on immunological and physicochemical properties allows the characterisation of unknown hPTH-peptides. Using this technique the heterogeneity of circulating hPTH-peptides in human plasma has been examined. Plasma extracts from healthy individuals, osteoporotic, hyperparathyroid and pseudohyperparathyroid patients were investigated. A uniform pattern in the heterogeneity of hPTH-peptides was detected. Using parathyroid adenoma as reference disease specific changes were characterised.
Improved diabetic control in insulin-dependent diabetics treated with insulin and glibenclamide
Authors: Burke B. J. , Hartog M. , Waterfield M. R.
Published: December 2008

Abstract. A randomized double blind trial of insulin and glibenclamide treatment vs insulin and placebo was carried out in 20 insulin-dependent diabetics. Nine patients were C-peptide secretors and all increased their C-peptide output during a 50 g OGTT at the end of the insulin and glibenclamide treatment period by a mean of 47%. At the same time their mean daily blood glucose fell from 8.4 ± 1.7 to 7.4 ± 1.5 mmol/l and their HbA1 from 8.1 ±0.5 to 7.5 ±0.9% (mean ± sd). There was no change in any of the measurements of diabetic control in C-peptide non-secretors and no evidence for any extrapancreatic effects of glibenclamide in this group of patients. Combined insulin and glibenclamide treatment may produce a useful improvement of diabetic control in insulin-dependent diabetics who still secrete some endogenous insulin, although further studies are required.
Modulation of aldosterone secretion in frusemide-induced hypokalaemia
Authors: Fujimaki Masaki , Nagahama Shusaku , Suzuki Hiroko , Saito Ikuo , Saruta Takao
Published: December 2008

Abstract. To study the effect of hypokalaemia in the regulation of aldosterone secretion, repeated injections of frusemide (3 mg/kg) plus saline with or without simultaneous infusion of potassium chloride (1 mEq/kg/h) were performed in 24 conscious female rabbits for 7 h. Without potassium supplementation, the plasma renin activity (PRA) remained elevated throughout the study, while an initial increase (1 h to 3 h) in plasma aldosterone (PA) gradually returned to normal with reduction of the serum potassium. In rabbits on potassium supplements to prevent the development of hypokalaemia, both PRA and PA remained elevated. The incremental aldosterone response to administration of potassium chloride, angiotensin II or ACTH, was considerably smaller in potassium-depleted rabbits than in potassium-repleted rabbits. These results suggest that serum potassium modulates the effects of angiotensin II or ACTH on aldosterone secretion, and that a certain level of potassium is necessary to maintain the aldosterone secretory capacity of the adrenal gland.
Steroid induced changes of the renal kallikrein-kinin system in rats
Authors: Bönner G. , Autenrieth R. , Marin-Grez M. , Speck G. , Gross F.
Published: December 2008

Abstract. In male Sprague-Dawley rats the influence of salt loading (1% NaCl), deoxycorticosterone acetate (2 × 15 mg/kg/day resp. 250 mg/kg sc), corticosterone (2 × 20 mg/kg/day sc) and adrenocorticosterone (0.5 mg/kg/day tetracosactid sc) on the activity of renal kallikrein and renal renin activity was investigated.

Salt loading lowered renal kallikrein activity, deoxycorticosterone stimulated its activity and in combination they had no effect on renal kallikrein activity. The time course of kallikrein stimulation by deoxycorticosterone showed no relationship to the escape phenomenon of the kidney from the sodium retaining effect of the mineralocorticoid hormone. Reduction of endogenous mineralcorticoid hormones by adrenalectomy caused a marked reduction of urinary and renal kallikrein activity.

Corticosterone suppressed the activity of the renal kallikrein-kinin system at the same time as the reduction in urinary aldosterone excretion. Adrenocorticotrophin caused the same decrease in the activity of renal kallikrein as corticosterone. Urinary aldosterone excretion, however, was significantly stimulated. Thus, the known positive correlation between kallikrein and aldosterone was missing.

In all experiments the urinary excretion of kallikrein correlated highly with the kallikrein activity measured in renal cortical tissue. However, no correlation was found between kallikrein and urine volume or urinary excretion of sodium and potassium. In our experiments no relationship between the activity of the renin-angiotensin system and that of the renal kallikrein-kinin system was observed. Furthermore, no clear relationship was found between systemic blood pressure and the activity of the renal kallikrein-kinin system.
Comparison of methionyl human growth hormone and pituitary growth hormone on somatic growth of hypophysectomized rats
Authors: Skottner A. , Forsman A. , Löfberg E. , Thorngren K.-G.
Published: December 2008

Abstract. In hypophysectomized male rats the biological effects of two batches of methionyl human growth hormone, Somatonorm®, (met-hGH), have been compared to those of human pituitary growth hormone, Crescormon® (hGH). The rats were treated with doses ranging from 10 mIU per day to 145 mIU per day for 10 days. The parameters studied were total weight gain, longitudinal bone growth, measured by the tetracycline method and indirect cartilage growth, measured by uptake of radioactive sulphate.

The results obtained demonstrated that Somatonorm® stimulated weight increase in a linear and dose-dependent way, similar to that seen with the native hormone. Longitudinal bone growth, measured by the tetracycline method and the growth of different cartilages, measured as uptake of radioactive sulphate, were also similar between the two hormones.
Changes in plasma thyrotrophin-releasing hormone, thyrotrophin, prolactin and thyroid hormone levels after intravenous, intranasal or rectal administration of synthetic thyrotrophin-releasing hormone in man
Authors: Mitsuma Terunori , Nogimori Tsuyoshi
Published: December 2008

Abstract. Changes in plasma thyrotrophin-releasing hormone (TRH), thyrotrophin (TSH), prolactin and thyroid hormone levels after iv, intranasal, or rectal administration of synthetic TRH were studied in man. The plasma TRH concentration increased with all three routes, but remained at higher levels for a longer time after intranasal or rectal administration, in contrast to the rapid decrease after iv administration. Plasma TSH, prolactin and thyroid hormone levels increased significantly after intranasal or rectal administration and also remained elevated for a longer period than iv administration.

These findings suggest that TRH administered intranasally or rectally enters the blood stream and stimulates TSH, prolactin and thyroid hormone release in man.
Abnormal growth hormone levels in insulin-dependent diabetic patients under continuous subcutaneous insulin infusion and intensified conventional treatment
Authors: Arias P. , Kerner W. , de la Fuente A. , Pfeiffer E. F.
Published: December 2008

Abstract. The present study was developed to assess the influence of prolonged blood glucose near normalization, achieved by means of continuous sc insulin infusion (CSII) or intensified conventional therapy (ICT) upon growth hormone (GH) secretion in insulin-dependent diabetes (IDD). Sixteen IDD patients (8 CSII-treated for 3–20 months and 8 under ICT) and 8 healthy control subjects were connected for 24 h to a newly developed, battery-powered glucose monitor. Diabetic patients received their usual food intake and insulin dosis. During the second hour after meals moderate exercise, walking at 1.5 km/h, was performed by all subjects. Blood samples for insulin and GH determination were taken before and 60, 120 and 180 min after meal ingestion.

Despite a similar degree of previous blood regulation, near normal glucose levels were attained only by the CSII group. Both ICT and CSII patients presented a marked postprandial hyperinsulinaemia. Abnormal GH levels were consistently registered in 4 CSII and 6 ICT patients 120 min after meal initiation. In consequence, both groups showed significantly elevated mean diurnal GH levels (controls: 1.1 ±0.3, ICT: 5.2 ± 0.9, CSII: 4.1 ± 1.1 ng/ml; P < 0.05).

According to these results, the pathologic GH secretion found in diabetic subjects is not fully normalized by tight control of blood glucose values.
Endocrinological effects of single daily ketoconazole administration in male beagle dogs
Authors: De Coster Roland , Beerens Dominiek , Dom Jef , Willemsens Gustaaf
Published: December 2008

Abstract. Some endocrinological effects of single daily oral administration of 150 mg ketoconazole for 15 days were investigated in 4 male beagle dogs. Plasma testosterone fell markedly within 3–4 h and then progressively returned to control concentrations by 10 h after drug administration. On the other hand, plasma 17α-hydroxyprogesterone, progesterone and 17α,20α-dihydroxyprogesterone increased within 3–10 h before returning to basal values after 24 h.

Plasma LH did not rise significantly though some high individual levels were noted. Plasma cortisol and oestradiol-17α levels were not significantly modified by the treatment.

These results confirm that a high therapeutic dose of ketoconazole, given orally once a day, transiently inhibits in vivo the 17–20 lyase enzyme of the testis, without modifying basal cortisol and oestradiol-17β plasma concentrations and that enzymatic inhibition still occurs after daily treatment for up to 2 weeks but remains transient and parallels the resorption profile of the drug so that normal plasma testosterone levels are observed from 10 to 24 h after drug intake. However, permanent inhibition of androgen biosynthesis might be obtained by the administration of high doses of ketoconazole given several times a day.
The influence of bromocriptine and transsphenoidal surgery on urinary androgen metabolite excretion in acromegaly
Authors: Roelfsema F. , Moolenaar A.J. , Frölich M.
Published: December 2008

Abstract. The urinary excretion of the androgen metabolites aetiocholanolone (E) and androsterone (A) as well as DHEA, 11-hydroxy-androsterone and the cortisol metabolites 11-oxo-aetiocholanolone and 11-hydroxy-aetiocholanolone in normoprolactinaemic and hyperprolactinaemic male and female acromegalics was studied and compared with that of appropriate control groups. In addition several plasma hormones were also measured. The growth hormone level in the patient group varied from 10–550 mU/l. The excretion of both 11-hydroxy-androsterone and DHEA was normal. The excretion of androsterone had decreased, while aetiocholanolone and cortisol metabolite excretion had increased. The ratio between aetiocholanolone and androsterone (E/A) excretion was significantly increased in all patient groups, but no correlation was found between the growth hormone level and the E/A ratio. Treatment with bromocriptine caused a decrease in the E/A ratio in patients with decreased growth hormone levels, but not in patients in whom the growth hormone level remained unchanged. After selective transsphenoidal removal of the pituitary adenoma the E/A ratio decreased significantly. The increased E/A ratio in untreated patients could not be attributed to eventual changes in plasma levels of cortisol, thyroxine, prolactin, testosterone or oestrogens. We therefore suggest that growth hormone is involved in androgen metabolism in acomegaly.
Somatomedin A in male puberty. Variation with age, maturity, growth and androgens
Authors: Krabbe Søren , Kastrup Knud William , Hummer Lotte
Published: December 2008

Abstract. Bioassayable somatomedin-A (SM-A) and serum concentrations of testosterone (T) and dehydroepiandrosterone (DHEA) were determined longitudinally in 26 normal boys during puberty. The mean trend of SM-A increased in relation to age, pubic hair development and peak height velocity (PHV) and significant correlations were observed with testicular volume, height velocity and T (all P < 0.001) but not with DHEA. In relation to growth SM-A increased mainly during 12 to 6 months prior to PHV but no further increase was seen in the 6 months thereafter. Thus pubertal growth and development have to be taken into account in the evaluation of changes in bioassayable SM-A concentrations in boys.
Effects of aging on prolactin release after stress in female and male rats
Authors: Milenković Ljiljana , Bogić Ljubica , Mušicki Biljana , Martinović Jovo V.
Published: December 2008

Abstract. Young adult and elderly male and female intact rats, as well as chronically ovariectomized (OVX) young and elderly female rats, were subjected to an acute stress by cutting the tip of the tail and prolactin (Prl) concentrations were measured in their blood collected by decapitation at various times thereafter. Maximum concentrations of the hormone were markedly lower in all the three groups of elderly rats than those found in the corresponding young animals, and appeared to occur with a delay in the females, but not in the males. In addition, the Prl-response to stress was attenuated in OVX animals regardless of their age. The result of these experiments, performed at two points on the age scale, suggests that in sexually mature rats of both sexes the stress-induced secretion of Prl is inversely related to the age of the animal and that the reverse relationship is retained in OVX females.
Familial elevation of serum thyroxine binding globulin in an Icelandic family
Authors: Sigurdsson G. A. , Arnason G. , Gudmundsson Th. V. , Kjeld M. , Franzson L. , Sigurdsson G.
Published: December 2008

Abstract. A kindred of four generations with inherited elevation of serum thyroxine binding globulin (TBG) is reported. To our knowledge this is the twelfth kindred reported with this disorder. Of the 35 family members studied, 10 females and 5 males had elevated serum TBG. The patients were clinically euthyroid. The pedigree data was consistent with an X-chromosome linked mode of inheritance.
Serum free T4, T3, rT3, 3,3'-diiodothyronine and 3',5'-diiodothyronine measured by ultrafiltration
Authors: Faber J. , Rogowski P. , Kirkegaard C. , Siersbæk-Nielsen K. , Friis T.
Published: December 2008

Abstract. A simple and accurate method for estimation of the free fractions (FFT) of T4, T3, rT3, 3,3'-diiodothvronine (3,3'-T2) and 3',5'-diiodothyronine (3',5'-T2) in serum is presented. The method is based on ultrafiltration of serum pre-incubated with tracers of high specific activity, followed by purification of the ultrafiltrate on small Sephadex columns. The addition of tracer only dilutes serum negligible (about 5%) and the ultrafiltration procedure only removes about 7% of the volume of serum, thus probably not disturbing the equlibrium between the free and protein bound fraction of iodothyronine.

Progressive reduction of tracer to less than 10% of the amount usually used did not reduce the FFT of any of the iodothyronines. In contrast, addition of T4 to serum led to an increase of all FFTs except that of 3',5'-T2. These data suggest that FFT of T4, T3, rT3 and 3,3'-T2 primarily is determined by the amount of T4 present in serum and that significant amounts of these iodothyronines are bound to TBG, whereas 3',5'-T2 possibly primarily is bound to albumin.

The median FFT of T4, T3, rT3, 3,3'-T2 and 3',5'-T2 in serum from euthyroid subjects (n = 38) was: 0.030, 0.29, 0.14, 1.10 and 1.07%, respectively. The corresponding median free concentrations in pmol/l were: 30, 4.79, 0.59, 0.44 and 0.77, respectively.

Pregnant women in 3rd trimester had normal levels of free T4, free T3 and free rT3, wheras the median free 3,3'-T2 was reduced in contrast to elevated median free 3',5'-T2.

Using the present method free T4 and free T3 discriminated almost completely hyper- and hypothyroid patients from controls, whereas some overlap to normal range was found concerning free rT3, free 3,3'-T2 and free 3',5'-T2.

Patients with liver cirrhosis or chronic renal failure (CRF) had profound changes in total serum concentrations of all iodothvronines studied, possibly due to the somatic disease. Despite this, almost all had unchanged free T4 and free T3 levels indicative of euthyroidism. The median free rT3 and free 3',5'-T2 were elevated in cirrhosis but unchanged in CRF, whereas median 3,3'-T2 was unchanged in both groups.
Oxygenation of 18-hydroxycorticosterone as the final reaction for aldosterone biosynthesis
Authors: Kojima Itaru , Ogata Etsuro , Inano Hiroshi , Tamaoki Bun-ichi
Published: December 2008

Abstract. Incubation of 18-hydroxycorticosterone with the sonicated mitochondrial preparation of bovine adrenal glomerulosa tissue leads to the production of aldosterone, as measured by radioimmunoassay. The in vitro production of aldosterone from 18-hydroxycorticosterone requires both molecular oxygen and NADPH, and is inhibited by carbon monoxide. Cytochrome P-450 inhibitors such as metyrapone, SU 8000. SU 10603, SKF 525A, amphenone B and spironolactone decrease the biosynthesis of aldosterone from 18-hydroxycorticosterone. These results support the conclusion that the final reaction in aldosterone synthesis from 18-hydroxycorticosterone is catalyzed by an oxygenase, but not by 18-hydroxysteroid dehydrogenase. By the same preparation, the production of [3H]aldosterone but not [3H]18-hydroxycorticosterone from [1,2-3H ]corticosterone is decreased in a dose-dependent manner by addition of non-radioactive 18-hydroxycorticosterone.