bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute effects of GnRF-induced gonadotrophin secretion upon ovarian steroid secretion in the ferret
Authors: Matson Christine , Donovan B. T.
Published: December 2008

Abstract. The effects of an increase in endogenous gonadotrophin secretion on the production of oestradiol, progesterone, androstenedione and testosterone by the ovaries of anaesthetized anoestrous and oestrous ferrets were followed. Gonadotrophin secretion was enhanced by the injection of gonadotrophin releasing factor (GnRF), and serial blood samples were collected over 9 h for hormone assay. Thyrotrophic hormone releasing factor (TRF) or acetic acid were injected for control purposes. The plasma content of oestradiol in oestrous females was significantly higher than during anoestrus, but secretion of this steroid was not increased by any means. The plasma concentration of progesterone in anoestrous females was significantly higher than during oestrus. It was increased by GnRF in anoestrous ferrets and less markedly in oestrous females. The plasma concentration of androstenedione was raised by GnRF to a greater extent during anoestrus than during oestrus. Testosterone was present in higher concentration in the plasma during anoestrus than during oestrus, and the level was increased by GnRF administration. These findings indicate that the ovaries of the anoestrous ferret secrete significant quantities of steroid hormones, and that they respond readily to gonadotrophic hormone.
Oestrogen agonistic effects of tamoxifen in the uterus of newborn guinea pigs after short and long treatment. Biological and histological studies
Authors: Pasqualini J. R. , Nguyen B.-L. , Mayrand C. , Lecerf F.
Published: December 2008

Abstract. Tamoxifen (TAM) alone or combined with oestradiol (E2) or progesterone (P) was administered to newborn guinea pigs (2 days old) for a short (2 days) or a long (12 days) treatment period. TAM alone provoked a great stimulatory effect on uterine growth and DNA content and the effect was particularly intense after the long treatment. These actions were markedly enhanced when TAM was administered together with E2. Following short treatment, the values of the uterine wet weights (mg ± sd) were as follows: control animals, 142 ± 15; animals treated with TAM, 298 ± 53; E2, 335 ± 15; (TAM + E2), 362 ± 16. The values after the long treatment were 177 ± 30, 555 ± 93, 709 ± 117 and 1263 ± 222, respectively.

Histological studies showed that TAM provoked morphological changes in both the endometrium and the myometrium. The effects were particularly great on the height of the luminal epithelial cells and on the uterine glands. After 2 days of treatment with E2, TAM and P, the thickness of the luminal epithelium, which was 13.5 μm ± 1.5 in the control animals, increased as follows: TAM, 19 μm ± 1.7; E2, 20.3 μm ± 3.3; (TAM + E2), 30.5 μm ± 5; P, 12 μm ± 0.9 and (P + TAM), 19.7 μm ± 1.2. The values after the 12 day treatment were: controls, 20.8 μm ± 1.8; TAM, 27.4 μm ±2.1; E2, 32 ± 3; (TAM + E2), 43 μm ± 5; P, 17.8 μm ± 1.2 and (P + TAM), 23.6 μm ± 1.5. After the short treatment TAM doubled the number of specific progesterone binding sites. It is concluded that TAM acts as a real oestrogen agonist in the uterus of newborn guinea pigs.
Women with prolactinoma – effect of pregnancy and lactation on serum prolactin and on tumour growth
Authors: Holmgren U. , Bergstrand G. , Hagenfeldt K. , Werner S.
Published: December 2008

Abstract. Thirty-five women with prolactinoma have been investigated during 41 pregnancies and 35 lactation periods. Nine of the women had a macroadenoma; 4 of them underwent transsphenoidal microsurgery and one was treated with external pituitary irradiation before pregnancy. All nine were given bromocriptine to induce ovulation. Four women with a microadenoma became pregnant without medical treatment, one shortly after pituitary microsurgery. The other 22 women were treated with bromocriptine only for varying periods before conception. Tumour complications developed in 7 women (20%); 3 had signs of optical nerve compression and 4 showed increased sella volume after pregnancy. All women with tumour complications had been treated with bromocriptine for less than 12 months before conception. Serum prolactin (Prl) was measured every four weeks during pregnancy and after cessation of lactation. In contrast to normal pregnancy, the mean serum Prl did not increase during the second and third trimester of pregnancy in women with pretreatment serum Prl levels above 60 μg/l. The lactation period did not have any harmful influence on tumour development. It is concluded that neither pretreatment serum Prl nor radiological changes of the sella turcica can predict tumour development during pregnancy. Treatment with bromocriptine for more than 12 months before conception seems to reduce the risk of tumour progress.
Rapid regression of macroprolactinomas by the new dopamine partial agonist terguride
Authors: Gräf K.-J. , Köhler D. , Horowski R. , Dorow R.
Published: December 2008

Abstract. Two patients with macroprolactinomas were treated with the partial dopamine agonist, terguride. The prolactin (Prl) levels were lowered very effectively and in both cases the clinical symptoms improved markedly during the first days of treatment. Computerized tomography (CT) and magnetic resonance imaging (MRI) follow-up studies showed distinct tumour shrinkages which were first documented by MRI within 2 weeks of treatment. Tumour residues were, however, still demonstrable by MRI after more than one year respectively 3 months of therapy. In principal, results from both imaging techniques were comparable with the exception of the one year follow-up study of patient 1. In CT no residual tumour mass was visible whereas MRI showed only little reduction when compared to the 30th week scan. Throughout the treatment terguride was well tolerated without any side effects up to a maximal daily dosage of 3 mg given orally. Presumably the partial agonistic features of terguride contributed to the good tolerance of the treatment as compared to that of full dopamine agonists like bromocriptine or lisuride. Thus, these preliminary results indicate that terguride may be a beneficial alternative in the treatment of prolactinomas and other hyperprolactinaemic states.
Stimulation of parathyroid hormone secretion by EDTA infusion – a test for the differential diagnosis of hypercalcaemia
Authors: Benson Lars , Rastad Jonas , Wide Leif , Åkerström Göran , Ljunghall Sverker
Published: December 2008

Abstract. A constant EDTA infusion of 24 mg/kg/h during 60–120 min was given to 26 patients with primary hyperparathyroidism (HPT), 8 patients with hypercalcaemia of other origin and 10 healthy control subjects. PTH and ionized calcium concentrations were measured at 5–10 min intervals. In all three groups the infusion caused a linear decrease in plasma ionized calcium. In both the HPT patients and the healthy subjects there was a prompt increase in the serum levels of parathyroid hormone (PTH) until a plateau was reached. The PTH response of the HPT patients appeared already within the hypercalcaemic range and the plateau value was attained at higher levels of PTH and ionized calcium than in the healthy subjects. The enhanced response distinguished half of the HPT patients with basal PTH values within the reference range from the healthy controls. The patients with nonhyperparathyroid hypercalcaemia displayed no increase in PTH values until the ionized calcium concentration was reduced far into or below the reference range. Thus the EDTA infusion permitted a complete differentiation between HPT and other causes of hypercalcaemia. In most cases an infusion over 30 min was sufficient for this purpose.
No association between retinopathy and insulin resistance in type 1 diabetes
Authors: Yki-Järvinen Hannele , Helve Eero , Laatikainen Leila , Karonen Sirkka-Liisa , Koivisto Veikko A.
Published: December 2008

Abstract. Intact endothelial cell function has been suggested to be important for insulin action. An association between retinopathy and insulin resistance has been found in type 2 diabetes. To evaluate, whether insulin resistance is related to retinopathy in insulin dependent diabetes, we examined 36 type 1 diabetic patients with various degrees of retinopathy: 7 patients had proliferative, 15 had background and 14 patients had no retinopathy. The three groups were matched for age, sex, body weight and insulin dose. Compared with patients with no retinopathy, those with proliferative retinopathy had a longer (P < 0.05) duration of diabetes (13 ± 3 vs 22 ± 3 years for no vs proliferative retinopathy), and higher (P < 0.05) serum creatinine (74 ± 4 vs 97 ± 8 μmol/l), triglyceride (0.69 ± 0.04 vs 1.02 ±0.17 mmol/l) and diastolic blood pressure (77 ± 3 vs 90 ± 10 mmHg) levels. The rate of insulinmediated glucose metabolism (1 mU euglycaemic insulin clamp) was virtually identical in each diabetic group (4.80 ± 0.42, 4.90 ± 0.36 and 4.98 ± 0.74 mg/kg/min) and 40% below that in 8 matched normal subjects (7.53 ± 0.53 mg/kg/min, P < 0.001).

In conclusion, proliferative retinopathy is related to long duration of diabetes, incipient nephropathy and hypertension. Insulin resistance characterizes the majority of patients with type 1 diabetes but is unrelated to retinopathy.
Maternal oestriol levels reflect placental function rather than foetal function
Authors: Perry L. , Hickson Rachel , Obiekwe B. C. , Chard T.
Published: December 2008

Abstract. We have examined the relationship between foetal levels of E3 and DHEA-SO4 and the birthweight of the child. Levels of these steroids do not relate to birthweight – although the concentration of DHEA-SO4 was marginally but not significantly higher in infants of lower birthweight. These findings suggest that the placental conversion of foetal precursors, and not the level of the precursors themselves, determines the concentration of E3 in the mother. Measurement of E3 as a clinical test reflects the function of both the foetus and the placenta.
The sensitivity of prolactin secretion to dopamine changes during pregnancy in mice
Authors: Swartz Stacey R. , Ogren Linda , Talamantes Frank
Published: December 2008

Abstract. Pituitary responsiveness to dopamine was investigated on several days of pregnancy in the mouse. Sera and anterior pituitary glands were obtained at 09.00 and 18.00 h on day 5 of pregnancy and at 09.00 h on days 12 and 18, and the pituitaries were incubated for 5 h in several concentrations of dopamine (0, 5 × 10−10—5 × 10−7 m). Serum prolactin (Prl) concentration was the highest on day 5 (18.00 h sample), followed by day 18 (09.00 h), day 5 (09.00 h) and day 12 (09.00 h). Pituitary responsiveness to dopamine was assessed on each day of pregnancy by determining the slopes of dose-response curves in which the Prl concentration of the medium was plotted as a function of dopamine concentration. The slope of the dose-response curve for pituitaries from day 12 or pregnancy was significantly steeper than the slopes of the curves for pituitaries from days 5 and 18, which did not differ from each other. These data suggest that the Prl secretion mechanism is more sensitive to inhibition by dopamine on day 12 of pregnancy, when serum Prl concentration is very low, than on days 5 or 18, when serum Prl concentrations are higher. One of the mechanisms by which circulating Prl concentrations are reduced to very low levels during midpregnancy in the mouse may be increased pituitary sensitivity to dopamine.
Postnatal development of brain TRH, serum TSH and thyroid hormones in the male and female rat
Authors: Gayo L. , Bonet B. , Herranz A. S. , Iglesias R. , Toro M.J. , Montoya E.
Published: December 2008

Abstract. The postnatal development of immunoreactive TRH in the central nervous system (CNS), serum TSH and thyroid hormones was studied in both male and female normal rats. While in most structures of the CNS, TRH increased until day 20–30, serum TSH values peaked at day 15 as did T4. Significant differences were also obtained between both sexes in these parameters. These data further support the fact that pituitary-thyroid axis maturation is independent of brain TRH.
Effects of oestradiol and progesterone on stress-induced secretion of prolactin in ovariectomized and/or adrenalectomized female rats
Authors: Milenković Ljiljana , Bogić Ljubica , Martinović Jovo V.
Published: December 2008

Abstract. Prolactin (Prl) secretion in response to an acute stress was studied in ovariectomized (OVX) and/or adrenalectomized (ADX) adult female rats, non-treated or injected sc with a single dose of 5 μg oestradiol-17β benzoate (OB) or 2 mg progesterone (P). The stress applied consisted of cutting the tip of tail of conscious animals. Radioimmunoassay was used to measure Prl in the serum prepared from blood collected by decapitation 10 min following the stress, i.e., at the point of maximum recorded Prl response. It was found that the capacity of the animals to secrete large quantities of Prl under stress was, when compared to that in intact controls, markedly reudced in OVX or ADX rats and substantially absent in OVX + ADX rats. A 10-fold increase of basal serum Prl, similar in magnitude to the increase in intact controls, was induced by the stress in OVX animals pretreated with OB. On the contrary, pretreatment of OVX animals with P resulted in a complete block of the Prl response to the stress. The stimulative effect of OB was greatly attenuated in stressed OVX + ADX rats. The results suggest that OB potentiates whereas P attenuates the stress-induced secretion of Prl in the female rat, and that the potentiating effect of OB is dependent on functionally intact adrenals.
Conversion of T4 to T3 in perfused liver of rats with carbontetrachloride-induced liver injury
Authors: Ikeda Tadasu , Ito Yasuo , Murakami Isao , Mokuda Osamu , Tominaga Masato , Mashiba Hiroto
Published: December 2008

Abstract. To evaluate the effect of hepatocellular damage on thyroid hormone metabolism, the conversion of T4 to T3 in the perfused liver of rats with carbontetrachloride (CCl4)-induced liver injury was investigated. The liver was perfused non-recyclically with a synthetic medium containing 10 μg/dl T4 for 30 min, and the T3 production and the conversion of T4 to T3 were examined.

The serum T3 level was significantly (P < 0.05) lower in liver-injury rats (72 ± 9 ng/dl) compared with controls (88 ± 10 ng/dl). The uptake of T4 (4.15 ± 0.85 μg/g/30 min), net T3 production (180 ± 48 ng/g/30 min), and conversion rate of T4 to T3 (4.4 ± 0.9%) in the perfused liver of liver-injury rats were similar to the values (3.78 ± 0.66 μg/g/30 min, 191 ± 31 ng/g/30 min, and 5.0 ± 1.0%) in control rats, whereas the release of T3 (12.7 ± 3.2 ng/g/30 min) in the effluent in injured livers was significantly (P < 0.05) lower than that (16.9 ± 3.0 ng/g/30 min) in control livers.

We concluded that in CCl4-induced liver-injury rats, the low serum T3 level may partly be due to the decreased release of T3 from liver cells after conversion of T4 to T3 rather than to a decreased conversion of T4 to T3.
Divergent effects of dietary chloride restriction on aldosterone biosynthesis and the renin-angiotensin system in rats
Authors: Müller Jürg , Seiler Heidi , Schwendener-Canlas Patricia , Henzi Cornelia
Published: December 2008

Abstract. The effects of dietary chloride restriction – alone or combined with sodium and postassium restriction – on aldosterone biosynthesis and the renin-angiotensin system were studied in rats. Treatment with a chloride-deficient diet led to a temporary decrease in the capsular adrenal conversions of corticosterone to 18-hydroxycorticosterone and aldosterone (manifest after 2 weeks but not longer apparent after 3 weeks), which was accompanied by a progressive rise in plasma renin activity and a moderate fall in plasma potassium. Combined restriction of sodium, potassium and chloride elicited a decreased activity of the enzyme(s) involved in late steps in aldosterone biosynthesis, an elevation of plasma renin activity to excessively high levels and a substantial hypokalaemia. Chloride repletion of these rats by the addition of NH4Cl or CaCl2 to their drinking fluid stimulated aldosterone biosynthesis while lowering plasma renin activity and raising plasma potassium. According to these observations, dietary chloride deficiency is another example of an experimental situation in which a high activity of the renin-angiotensin system contrasts with an unchanged or suppressed aldosterone biosynthesis. Most likely, this divergence is at least partly due to hypokalaemia which is induced during long-term chloride deficiency by a yet unknown mechanism.
Neonatal hyperthyroidism causes impairment in submandibular gland-nerve growth factor (SMG-NGF) ontogeny in mice
Authors: Lakshmanan J.
Published: December 2008

Abstract. The effect of neonatal hyperthyroidism on submandibular gland (SMG) nerve growth factor (NGF) concentrations was studied in female Swiss-Webster mice. For this purpose, newborn female pups were treated with thyroxine (T4, 0.4 μg/g body weight/day) from birth through day 6, while their littermate pups were treated with similar volumes of vehicle. Animals were sacrificed on days 7, 15, 21, 31 and 71. Somatic growth (body weight and nose to rump length), serum T4 and T3 concentrations, and SMG and serum-NGF concentrations were measured. The data indicate that neonatal hyperthyroidism a) causes inhibition of somatic growth; b) induces alterations in normal ontogenic patterns of serum T4 and T3; c) impairs the developmental rise in SMG-NGF concentration and d) transiently increases serum-NGF levels.
Effects of different photoperiods on circulating levels of melatonin and N-acetylserotonin in the female rabbit
Authors: YoungLai E. V. , Pang S. F. , Brown G. M.
Published: December 2008

Abstract. The influence of different photoperiods on the secretion of metatonin and N-acetylserotonin (NAS) in the female rabbit was investigated. Under all photoperiodic conditions, 12-h light: 12-h dark (12L:12D), 2L:22D and 22L:2D, mean melatonin levels were higher during the scotophase. By contrast, mean NAS levels were 2–6-fold greater in the photophase compared to levels in the scotophase. This dissociation of circulating melatonin and NAS suggests that in the rabbit melatonin secretion is tightly controlled by the scotoperiod and NAS is probably produced by and originates from other organs as well as the pineal.
Haemodynamic role of vasopressin released during Finnish sauna
Authors: Bussien J. P. , Gaillard R. C. , Nussberger J. , Waeber B. , Hofbauer K. G. , Turnill D. , Brögger R. , Brunner H. R.
Published: December 2008

Abstract. The effect of vasopressin released during Finnish sauna on blood pressure, heart rate and skin blood flow was investigated in 12 healthy volunteers. Exposure to the hot air decrease body weight by 0.6 to 1.25 kg (mean = 0.8 kg, P < 0.001). One hour after the end of the sauna sessions, plasma vasopressin was higher (1.7 ± 0.2 pg/ml, P < 0.01 mean ± sem) than before the sauna (1.0 ± 0.1 pg/ml). No simultaneous change in plasma osmolality, plasma renin activity, plasma norepinephrine, epinephrine, cortisol, aldosterone, beta-endorphin and metenkephalin levels was observed. Despite the slight sauna-induced elevation in circulating vasopressin, intravenous injection of the specific vascular vasopressin antagonist d(CH2)5Tyr-(Me)AVP (5 μg/kg) 1 h after the sauna had no effect on blood pressure, heart rate or skin blood flow. These data suggest that vasopressin released into the circulation during a sauna session reaches concentrations which are not high enough to interfere directly with vascular tone.
Infarction of a growth hormone-secreting macroadenoma during a TRH test
Authors: Lever E. G. , Butler J. , Moore P. , Cox T. C. S. , Maccabe J. J.
Published: December 2008

Abstract. Pituitary infarction occurring immediately after TRH injection (200 μg) is reported in a patient with gigantism due to a growth hormone-secreting pituitary macroadenoma. Evidence of infarction was seen in CSF and in serial CT scans. Regression of symptoms and sign of acromegaly, abolition of abnormal growth hormone secretion, and virtually complete anterior and partial posterior pituitary failure rapidly followed. The infarction was probably initiated by a hypertensive response to TRH. TRH testing in acromegalic subjects may require smaller doses of TRH to avoid unwanted pressor responses.
Interference with thyrotropin receptor antibody determination by a spuriously occurring anti-bovine TSH antibody
Authors: Iitaka Makoto , Tanikawa Toshinori , Sakatsume Yoshiki , Yanagisawa Morifumi , Hara Yoshihito , Ishii Jun
Published: December 2008

Abstract. Abnormally negative values of thyrotropin binding inhibitor immunoglobulin (TBII) were found in the sera from a patient with Graves' disease. This was due to the presence of potent bovine TSH (bTSH) binding activity in the sera. This activity was demonstrated to be in immunoglobulin G (IgG) with a λ light chain isotype, which was shown to have an affinity for bTSH with a Ka value of 3.5 × 1010 m−1 and a maximum binding capacity of 1.1 × 10−14m/mg IgG. F(ab')2 fragments obtained through pepsin digestion from the patient's IgG retained bTSH binding activity. [125I] bTSH binding to this IgG was inhibited by the TSH receptor. The inhibition was not completely competitive, suggesting the presence of different binding sites for this IgG and the TSH receptor on the TSH molecule. This IgG, however, could not bind labelled human TSH (hTSH). Since neither TSH nor other pituitary derivatives had ever been given to the patient, this bTSH binding activity was considered to be due to a spuriously occurring anti-bTSH antibody.
Immunoreactive gastric inhibitory polypeptide and K cell hyperplasia in obese hyperglycaemic (ob/ob) mice fed high fat and high carbohydrate cafeteria diets
Authors: Bailey C. J. , Flatt P. R. , Kwasowski P. , Powell C.J. , Marks V.
Published: December 2008

Abstract. The effect of diet composition on plasma and intestinal concentrations of immunoreactive gastric inhibitory polypeptide (GIP) and intestinal K cell density was examined in obese hyperglycaemic (ob/ob) mice. The mice were reared from 3 to 11 weeks of age on either stock diet, a high fat (HF) cafeteria diet or a high carbohydrate (HC) cafeteria diet. The HF cafeteria diet increased the concentration of GIP in plasma (75%) and in the intestine (118%) and increased the density (54%) of GIP-secreting K cells in the upper jejunum compared with the stock diet. Plasma and intestinal GIP concentrations were not significantly altered by the HC cafeteria diet, although the density of K cells in the upper jejunum was increased (45%). The extent of hyperglycaemia and hyperinsulinaemia in ob/ob mice was not significantly altered by the HF and HC cafeteria diets. The results indicate that an increased amount of dietary fat chronically stimulates the production and secretion of GIP, and enhances intestinal K cell density in ob/ob mice.
Development of ovarian follicles during lactation in rats
Authors: van der Schoot P. , de Greef W.J.
Published: December 2008

Abstract. Ovarian follicular development was studied during lactation in rats. At an early stage of lactation (day 7) the ovaries showed only small follicles in agreement with the expected 'follicular quiescence' during lactation. However, at a more advanced stage of lactation (day 14), there were large follicles which were capable of ovulation in response to exogenous gonadotropins. Unilateral ovariectomy early during lactation (day 2) resulted in compensatory follicular development in the remaining ovary. However, doubling of the number of large follicles per ovary had not yet occurred by day 13. Unilateral ovariectomy caused a significant prolongation of the delay of embryonic implantation in pregnant lactating rats: this probably reflected delay of the development of sufficiently large numbers of oestrogen-producing follicles for this process. Unilateral ovariectomy did not affect the length of lactational pseudopregnancy. The findings indicate that 'follicular quiescence' during lactation in rats is limited to the very first period after parturition. This limitation may result from the relative ineffectiveness of suckling to suppress the secretion of FSH. In this respect, ovarian follicular development in rats differs from that in many other species, including primates and man.
There is evidence that amniotic fluid arginine vasopressin is a marker for foetal stress in rhesus erythroblastosis
Authors: Stegner H. , Fischer K. , Pahnke V. G. , Kitschke H.J. , Commentz J. C.
Published: December 2008

Abstract. In response to different stress stimuli the foetal neurohypophysis releases arginine vasopressin (AVP). Part of the AVP is cleared from circulation by urinary excretion into the amniotic fluid (AF). Increased AF AVP levels may therefore indicate foetal stress, all the more because AF AVP solely is of foetal origin. We therefore studied AF AVP levels in 13 patients with rhesus erythroblastosis from 22 to 34 weeks of gestation. Twenty-eight patients from 14 to 34 weeks of gestation served as controls. The AVP levels were measured by RIA. Spectral absorption curves were performed and delta/E values determined at 450 nm. Mean AF AVP levels in controls were 2.39 pg/ml and were not normally distributed. There was no significant change in AF AVP levels with different gestational age. If in rhesus erythroblastosis patients the delta/E value was low (n = 7; × = 0.048 ± 0.007 se), the AF AVP values were not increased. If the delta/E values were within zone III (n = 6; × = 0.22 ± 0.035 se), indicating severe haemolysis, the AF AVP levels were significantly elevated (4.7 pg/ml ± 0.51 se; P = 0.001). Linear regression analysis showed a significant correlation between delta/E and AF AVP values (P = 0.05; y = 1.94 ± 10.88 x). We conclude that there is evidence for the role of AF AVP as a marker for foetal stress in rhesus erythroblastosis.
Modulation of immunoreactive somatomedin-C levels by sex steroids
Authors: Caufriez Anne , Golstein Jacqueline , Tadjerouni Ali , Bosson Daniele , Cantraine Francis , Robyn Claude , Copinschi Georges
Published: December 2008

Abstract. Among 28 menstruating women tested once randomly during the cycle, somatomedin-C (Sm-C) values were lower in the 10 women in normal follicular phase than in the 10 women in normal luteal phase or the 8 women with hyperandrogenism. Among these 28 subjects, Sm-C showed a positive correlation with testosterone and a positive correlation of borderline significance with oestradiol. A positive correlation was also evidenced between Sm-C and In progesterone among the 20 women of this group who were not hyperandrogenic. In 5 other normal women investigated daily throughout an entire menstrual cycle, Sm-C concentrations were higher during days +4 to +9 of this cycle (luteal phase) than during days −3 to −8 (follicular phase). In another group of 21 healthy women, Sm-C values were increased during medroxyprogesterone acetate (150 mg trimestrially) treatment. In 7 normal men, Sm-C decreased during ethinyl-oestradiol (1 mg daily for 5 days) administration. These findings suggest that circulating Sm-C levels are modulated by variations of sex steroids which occur during the menstrual cycle as well as by pharmacological doses of oestrogens and progestagens.
Cushing's disease coexisting with a single macronodule simulating adenoma of the adrenal cortex
Authors: Leiba Sara , Shindel Bella , Weinberger Itzhak , Fuchs Jacobs , Rotenberg Zvi , Mor Celia , Kaufman Haiuta
Published: December 2008

Abstract. A rare case of Cushing's disease coexisting with a single macronodule simulating adenoma of the adrenal cortex is presented. The basal and dynamic tests supported the diagnosis of Cushing's disease, whereas the CT-scan, ultrasound and iodocholesterol uptake were suggestive of a left adrenal adenoma. Treatment consisted of extirpation of the nodular gland followed by pituitary irradiation. The examination revealed a single macronodule with no histological membrane, surrounded by hyperplastic adrenocortex. Together with the three similar ones reported in the literature this case suggests that nodular hyperplasia may be an intermediary stage between diffuse hyperplasia and the appearance of an autonomous adenoma after long-term stimulation of the hyperplastic gland.
Insulin release and pancreatic insulin is reduced in young prediabetic BB rats
Authors: Svenningsen Annette , Dyrberg Thomas , Markholst Helle , Binder Christian , Lernmark Åke
Published: December 2008

Abstract. The pancreases of approximately 50 days old diabetes-prone BB/Hagedorn (BB/H) and of the genetically closely related, but non-diabetic BB w-subline (control BB) rats were perfused to determine the capacity of D-glucose to release insulin before the expected development of diabetes. The BB/H rats were from a colony with 82–84% incidence of insulin-dependent diabetes mellitus (IDDM) by 140 days of age. The total amount of insulin released from the BB/H rat pancreas during stimulation with 20 mmol/l D-glucose was reduced by nearly 50% (P <0.01). The initial peak of insulin release was similar between the two groups of animals, whereas the amount of insulin released during the second peak accounted for the diminished release (P < 0.01). The extractable pancreatic insulin was 30% (P < 0.05) less in the BB/H rats. Total insulin release expressed relative to the pancreatic insulin content, was therefore not different between the two groups. It is concluded that about 20–40 days before the mean age of clinical onset of IDDM in BB/H rats, the capacity to release insulin in response to D-glucose is reduced along with a diminished pancreatic insulin content. This abnormality seems to be preceded only by islet cell surface antibodies but not by insulitis.
Insulin resistance in human liver cirrhosis is not modified by porto-systemic surgical shunt
Authors: Cavallo-Perin P. , Bruno A. , Nuccio P. , Dall'omo A. M. , Fronda G. R. , Avagnina P. , Molino G. , Bozzo C. , Pagano G.
Published: December 2008

Abstract. Cirrhosis of the liver is characterized by glucose intolerance and hyperinsulinaemia. It is considered an insulin resistant state with both a receptor and a post-receptor defect of insulin activity. It would appear that reduced hepatic degradation rather than increased B-cell production is responsible for hyperinsulinaemia. The effect of surgical portosystemic shunt on insulin resistance was studied in 18 cirrhotics with impaired glucose tolerance (12 males, 6 females; mean age 46.9 ± 0.7 years) by measuring: glucose production (3H-glucose infusion), glucose utilisation (euglycaemic clamp at ~ 100, ~ 1000 and ~ 10000 μU/l), plasma insulin and C-peptide levels, and liver function indices (serum bilirubin, albumin, ALT, GGT) before and 2 months after surgery. Liver sorbitol clearance was also employed to measure variations in the functional liver plasma flow induced by the shunt. No significant changes were noted in: glucose production (1.94 ± 0.17 sem vs 1.96 ± 0.17 mg/kg/min), glucose utilisation (metabolic clearance rate: 3.32 ± 0.48 vs 3.42 ± 0.43 at ~ μU/ml; 9.70 ± 1.0 vs 9.16 ± 0.9 at~ 1000 μU/ml; 10.92 ± 1.1 vs 11.07 ± 0.8 ml/kg/min at ~ 10000 μU/ml), fasting plasma insulin, C-peptide and C-peptide/insulin molar ratio (4.66 ± 0.47 vs 5.50 ± 0.54), and the liver function indices. By contrast, there was a significant decrease in functional liver plasma flow (813 ± 34 vs 604 ± 34 ml/min, P < 0.001). These results suggest that surgical shunt does not modify the mechanisms and the degree of insulin resistance in human liver cirrhosis and that hyperinsulinaemia can not be primarily referred to change of liver perfusion, but is most probably related to liver cell damage.
The relative importance of glucocorticoids and mineralocorticoids in the development of adrenal regeneration hypertension in rats
Authors: Kenyon C.J. , Clark S. A. , Hannah J. A. M. , Holloway C. D. , Ingram M. C. , Lindop G. , Towrie A. , Ball S. G.
Published: December 2008

Abstract. The adrenocortical tissue which regenerates after adrenal enucleation, and contralateral uninephrectomy and adrenalectomy, resembles histologically zona fasciculata tissue which normally synthesises glucocorticoids. However, increases in blood pressure after enucleation (adrenal regeneration hypertension – ARH) were preceded by a rise in exchangeable body sodium similar to that found with mineralocorticoid-induced hypertension (e.g. DOC/salt rat model). Glucocorticoid involvement in ARH rats was tested, firstly by infusing dexamethasone into control and ARH rats to see whether ACTH suppression would lower blood pressure by reducing adrenocortical activity and, secondly, by infusing dexamethasone into rats with intact adrenals to see whether conditions for ARH (i.e. uninephrectomy and/or saline consumption) pre-disposed rats to the hypertensinogenic properties of glucocorticoids. Low-dose dexamethasone infusions (10 μg/day for 5 days) in ARH rats did not affect blood pressure but in control animals caused a significant (P < 0.01) increase from 128 ± 3 to 151 ± 5 mmHg. Corticosterone, 18-hydroxycorticosterone and deoxycorticosterone plasma concentrations were suppressed in both groups by dexamethasone treatment; plasma renin concentrations were lower in ARH rats than in controls. Uninephrectomy or 1% NaCl as drinking fluid did not affect the blood pressure rise induced by sc infusion of 10 μg dexamethasone/day for 14 days in rats with intact adrenals. The temporal relationship between blood pressure changes and exchangeable body sodium in ARH rats resembles that in mineralocorticoid-induced hypertension. Glucocorticoid, unlike mineralocorticoid, induced hypertension is not affected by a reduction in renal mass or increased sodium intake.
Presence of oestrogen receptors in human blood mononuclear cells and thymocytes
Authors: Weusten J. J. A. M. , Blankenstein M. A. , Gmelig-Meyling F. H.J. , Schuurman H.J. , Kater L. , Thijssen J. H. H.
Published: December 2008

Abstract. We studied oestrogen binding sites in blood mononuclear cells from healthy blood donors, patients with leukaemia or systemic lupus erythematosus, and in thymocytes, using the dextran-coated charcoal assay and Scatchard analysis of binding data. Using 3H-labelled oestradiol as ligand, inaccurate results were obtained which could be related to the low amounts of binding sites. Using 125I-labelled ligand, saturable oestradiol binding sites could be demonstrated in low amount (mean value 2.1 fmol/mg of cytosolic protein) and high affinity (mean Kd value 0.26 nm; mean Ka value 3.85 × 109 m−1). The binding could be inhibited by unlabelled oestradiol but not with oestrone, dihydrotestosterone, cortisol and the progestin-receptor ligand Org 2058. We conclude that blood mononuclear cells and thymocytes contain true oestrogen receptors. This conclusion supports current hypotheses on the involvement of such receptors in oestrogen-mediated modulation of the immune system.
Effects of cisplatin on the mouse testis
Authors: Vawda A. I. , Davies A. G.
Published: December 2008

Abstract. This study reports the effects of cisplatin, an anti-cancer agent, on testicular function in mice. A single dose of 8 mg cisplatin/kg body weight administered to MF1 mice by an ip injection reduced the number of resting primary spermatocytes only. These cells decreased by 69% 3 days after treatment, 76% 4 days after treatment, 95% 5 days after treatment and 89% 6 days after treatment. Sperm motility was reduced by an average of 36% and the rate of testicular DNA synthesis by 36%. A body weight loss of 10% was also recorded. Cisplatin did not affect the rate of protein synthesis by the testis; nor was there a change in testicular protein, RNA and DNA contents. The weights of the testis, seminal vesicle and epididymis were also not affected by treatment. No significant change was noted in epididymal sperm number or in the proportion of abnormal sperm. Since cisplatin did not affect stem cell spermatogonia, there appears to be no danger of permanent sterility. The effect on spermatogenesis is probably transient and reversible after withdrawal of the drug.
Splanchnic extraction of oestrone and oestradiol and production of oestrone sulphate in man
Authors: Myking Ole , Aakvaag Asbjørn , Ohm Ole Jörgen
Published: December 2008

Abstract. The plasma concentrations of oestrone (Oe1), oestradiol (Oe2) and oestrone sulphate (Oe1S) were measured in the femoral artery (FA), femoral vein (FV) and hepatic vein (HV) in seven men and three postmenopausal women undergoing catheterization for the evaluation of cardiac arrhytmias. None of the persons had congestive heart failure; conventional liver function tests were normal, and they were without any medication. The plasma concentration (mean ± sd) for Oe1 was 34.6 ± 19.5 pm in HV, 134 ± 71.6 pm in FV and 93.4 ± 48.5 pm in FA. The plasma concentration of Oe2 was 29.9 ± 19.7 pm in HV, 80.3 ± 42.7 pm in FV and 55.2 ± 28.1 pm in FA. The results support the concept of peripheral formation of Oe1 and Oe2 and hepatic removal. The plasma concentration of Oe1S was 980 ± 469 pm in HV, 945 ± 463 pm in FV and 937 ± 461 pm in FA. The small difference in plasma level of Oe1S between FA and FV was insignificant. In all persons the plasma level of Oe1S was higher in HV than in FA and FV (2P <0.01) indicating a net formation of Oe1S in the splanchnic area.
Pharmacokinetics in the human of a new synthetic vasopressin and oxytocin uterine antagonist
Authors: Lundin Stefan , Åkerlund Mats , Fagerström Per-Olof , Hauksson Arnar , Melin Per
Published: December 2008

Abstract. The pharmacokinetics in the human of 1-deamino-2-D-Tyr(OEt)-4-Thr-8-Orn-vasotocin (dE-TVT), was studied after iv and intranasal administration in 11 subjects at 12 experiments each route. The plasma concentration of the analogue was analysed by means of an arginine vasopressin antibody, which cross-reacted with dE-TVT to 4.7%. When given intravenously as bolus injection (10 nmol/kg/body weight), the total body clearance amounted to 0.623 ± 0.099 (sem) 1/h kg and the half-life to 16.2 ± 2.4 min. After intranasal administration (100 nmol/kg/body weight), the bioavailability was 10.5 ± 2.9%. Peak concentrations in plasma appeared 2–8 min after iv and 10–45 min after intranasal administration. At the end of an observation period of 2 h measurable amounts in plasma were still found in one of the iv and seven of the intranasal experiments. It is concluded that the moderately long half-life is suitable for the treatment of hospitalized patients in premature labour where promising results with intravenous infusion (50 μg/min) of dE-TVT have been obtained. It is still uncertain whether or not the absorption of dE-TVT is sufficient for intranasal administration to out-patients with uterine hyperactivity in late pregnancy and to patients with primary dysmenorrhoea, where significant relief of symptoms were seen after iv administration (10 μg/kg body weight).
Abnormal beta-endorphin and beta-lipotropin responses to TRH and LRH administration in primary and secondary affective disorders
Authors: Brambilla E. , Petraglia F. , Facchinetti F. , Genazzani A. R.
Published: December 2008

Abstract. Anomalous anterior pituitary hormone responses to acute administration of TRH and LRH have previously been observed in patients with primary affective disorders (PAD), with TRH eliciting GH, FSH and LH rises, and LRH eliciting GH and Prl rises. We examined whether the same unusual responses were present also for beta-endorphin (β-EP) and beta-lipotropin (β-LPH) in 15 PAD patients, in 9 patients with secondary affective disorders (SAD), and in 7 controls. TRH (500 ug iv) elicited rises of β-EP plasma levels in 5 PAD and 2 SAD patients, and of β-LPH in 4 PAD and 3 SAD patients. LRH (150 ug iv) elicited rises of plasma β-EP levels in 2 PAD and 2 SAD patients, and of β-LPH in 5 PAD and 2 SAD patients. No rises of β-EP and β-LPH plasma levels were observed in PAD patients after saline administration, nor in the controls after TRH, LRH or saline administration.
Characterization of insulin-binding to the hepatoma cell line H35
Authors: de Vries C. P. , van der Veen E. A.
Published: December 2008

Abstract. We have studied the characteristics of insulin-binding to its receptor in H35 hepatoma cells. Insulin-binding was time, temperature and pH dependent. Optimum pH was 8.0–8.2. Binding at 21°C reached a steady state after 90 min of incubation at a level of 30.0 ± 2.6% per mg protein. Pre-incubation of the cells with unlabelled exogenous insulin resulted in a decrease of insulin-binding which was time and concentration dependent. Pre-incubation with 10 μg/ml for 24 h resulted in a decrease to 35–40% of initial binding. Scatchard plots of the binding data were curvilinear in control as well as in down regulated cells. Analysis of the Scatchard plots revealed that decrease of insulin-binding to down regulated cells was due to a decrease of insulinbinding sites, while affinity constants did not change.
Adenylate cyclase activity in rat corpora lutea evidence for a rapid development of the regulatory Ns-protein
Authors: Rosberg Sten , Norjavaara Ensio , Baum Monica Sender , Khan Iqbal
Published: December 2008

Abstract. Adenylate cyclase activity was studied in membranes from isolated corpora lutea of defined ages obtained from pregnant mare's serum gonadotropin treated rats and the effects of luteinizing hormone (LH), isoproterenol, guanylylimidodiphosphate (Gpp (NH)p), fluoride and forskolin were compared. The effect of LH on adenylate cyclase activity increased with the luteal age up to nine days of age, while the effect of isoproterenol increased dramatically during the first days, reaching a maximum at 2–3 days of age and then declined. Forskolin potentiated the effects of both LH and isoproterenol without affecting the patterns of age-dependency. The effect of forskolin itself was fairly constant during the luteal phase, indicating a relatively constant amount of the catalytic unit in the corpus luteum. The effects of fluoride and Gpp(NH)p on the other hand increased markedly during the first days and then remained constant for the rest of the period studied. These results suggest that the regulatory Ns-protein develops during the first days of luteal life. It is speculated that the close correlation between the development of β-adrenergic response and the development of Ns-protein are causally related.
Influence of the assay method used on the selection of the most active forms of FSH from the human pituitary
Authors: Wide Leif , Hobson Bruce
Published: December 2008

Abstract. The biological properties of different forms of human pituitary FSH, varying in their molecular charge, were investigated. FSH in two individual human pituitaries and a pool of 30 human pituitaries was extracted and subjected to electrophoresis. From each electrophoresis 14 consecutive fractions with the highest RIA activity were examined with in vitro and in vivo bioassays. The in vitro assay was based upon the estimation of oestradiol produced by cultured Sertoli cells from 10 day old rats. The in vivo bioassay was an hCG augmented test using immature female mice injected on 3 consecutive days. The increase in ovarian weight was the index of response. Both in the individual and in the pooled pituitary material the less negatively charged forms had the highest activity in the in vitro bioassay. In contrast, the more negatively charged forms had the highest activity in the in vivo bioassay. Forms of FSH from each of the two individual pituitary extracts were pooled according to their migration rate and injected iv into mice. The amount of FSH remaining in the circulation of the mouse after 1 h was related to the molecular charge. The highest value was obtained with the pool containing the more negatively charged forms of the hormone. The results indicate that the disappearance rate of the FSH molecule is a dominant factor in the in vivo bioassay. A consequence of these observations will be that the assay method chosen to monitor the purification of FSH will have a major influence on the biological properties of the final preparation.
Hyperthyroidism due to non-tumoural inappropriate TSH secretion
Authors: Williams Gareth , Kraenzlin Marius , Sandier Laurence , Burrin Jacky , Law Adam , Bloom Stephen , Joplin G. F.
Published: December 2008

Abstract. Inappropriate hypersecretion of TSH was investigated in a 25 year old man whose hyperthyroidism had relapsed 4 years after subtotal thyroidectomy. Serum TSH levels were further increased by both TRH and metoclopramide and were partially suppressed by triiodothyronine (120 μ/day). The serum α-subunit: TSH molar ratio was < 1.0, and computerised axial tomography showed no evidence of a pituitary tumour. These features are characteristic of inappropriate TSH secretion due to thyrotroph resistance to thyroid hormones. A long-acting somatostatin analogue (SMS 201-995), 50 μg injected sc twice-daily for three days, suppressed TSH levels and nearly normalised thyroid hormone levels. Somatostatin analogues may be therapeutically useful in thyrotoxicosis due to non-tumoural inappropriate TSH hypersecretion.
Conversion of thyroxine to 3,5,3'-triiodothyronine in several rat tissues in vivo: the effect of hypothyroidism
Authors: van Doom Jaap , Roelfsema Ferdinand , van der Heide Daan
Published: December 2008

Abstract. The local conversion of thyroxine (T4) to 3,5,3'-triiodothyronine (T3) has been recognized as a source of T3 at various sites in euthyroid rats. The present study was designed to evaluate the effect of hypothyroidism on the source and quantity of T3 at several of these sites (liver, cerebral cortex (Cx), thymus, testis, brown adipose tissue). For this purpose intact euthyroid rats and radiothyroidectomized (RTx) rats received a continuous iv infusion of [125I]T4 and [131I]T3 until isotopic equilibrium was attained. In addition to the labelled iodothyronines, RTx rats received a continuous iv infusion of 0.75 μg T4/day, in order to maintain a defined hypothyroid state. At the end of the infusion period the animals were bled and perfused, and homogenates of the various organs were prepared. The mean plasma T4 and T3 levels in T4-maintained RTx rats, as measured by RIA, were 1.5 μg/dl and 15 ng/dl (euthyroid values: 5.2 μg/dl and 48 μg/dl, respectively). The plasma and tissue homogenates were processed for thin layer chromatography and the [125I]T4, [125I]T3 and [131I]T3 levels determined. From these data the concentrations of T4, total T3 and T3 derived from local T4 to T3 conversion (LcT3(T4)) in tissue could be calculated. The relative mean contribution of LcT3(T4) to the total T3 in Cx (75%), thymus (31%), testis (43%) and brown adipose tissue (65%) from hypothyroid rats was higher than that determined for euthyroid animals (66%, 19%, 29% and 27%, respectively). The reverse was found for the liver (15% vs 39%). As a consequence, hypothyroidism led to a substantial loss of intracellular T3 in the liver (about 80%), whereas in all other tissues investigated the decrease in total T3 was less. In spite of the low intracellular T4 levels in hypothyroid rats, the quantity of LcT3(T4) in brown adipose tissue had increased significantly. This was not the case in the other tissues investigated. However, as found for brown adipose tissue, the ratio between LcT3(T4) and T4 found for Cx, thymus and (although not statistically significant) testis was higher in hypothyroid rats than in euthyroid animals, again suggesting a higher degree of in vivo T4 to T3 conversion in the hypothyroid state. These results strongly suggest that local factors play an important role in the regulation of intracellular T3 levels.