bluuebunny/crossref_metadata_2025 huggingface dataset:
Conversion of 22S-hydroxy-cholesterol and its effect on the metabolism of other sterols in rat adrenal cells and bovine adrenal mitochondria
Authors: Huijmans J. G. M. , Degenhart H. J. , Kortleve D. J.
Published: December 2008

This study provides evidence that 22S-OH-cholesterol inhibits the conversion of 25-OH-cholesterol but has no effect on the conversion of 22R-OH-cholesterol. The latter sterol is an intermediate in the cholesterol side-chain cleavage, whereas for the conversion of 25-OH-cholesterol into pregnenolone the complete side-chain cleaving enzyme system is necessary. This complements a previous study in which it was shown, that 22S-OH-cholesterol has an inhibitory effect on the ACTH-induced conversion of cholesterol into corticosterone in isolated rat adrenal cells.

The available evidence thus suggests an inhibition by 22S-OH-cholesterol of the first step in the cholesterol side-chain cleavage.

The results, obtained from the experiments with rat adrenal cells and with bovine adrenal mitochondria, allow the hypothesis, that a causal relationship exists between conversion of 22S-OH-cholesterol and production of corticosterone, respectively pregnenolone.

We conclude, that 22S-OH-cholesterol is a substrate for steroid production in the adrenal cell. This sterol inhibits the ACTH-stimulated corticosterone production. The site of this inhibition is located at one of the first steps in the cholesterol side-chain cleavage, probably the binding of cholesterol to the cytochrome P450-complex.
Immunological aberration in primary hyperparathyroidism
Authors: Elias Alan N. , Sharma Brahma S. , Stokes John D. , Valenta Lubomir J.
Published: December 2008

Altered immunological reactivity in primary hyperparathyroidism is suggested by the strong association between this disorder and malignancy. The present study was carried out to determine whether altered lymphocyte proliferation in response to common mitogens (PHA, Con-A, PWM) exists in primary hyperparathyroidism, and, if so, whether the abnormality resides in the lymphocytes or in humoral factors present in the plasma of patients with hyperparathyroidism. Ficoll-Hypaque purified lymphocytes from 6 patients with primary hyperparathyroidism and 4 normal volunteers were stimulated with PHA, Con-A and PWM in the presence of plasma from patients with primary hyperparathyroidism and normal AB+ plasma. The incorporation of [3H]thymidine in unstimulated (control) and stimulated cultures was determined. The results demonstrate that lymphocyte proliferation was significantly higher when both patients' and normal lymphocytes were stimulated with mitogens in the presence of patients' plasma. These findings suggest that plasma from patients with primary hyperparathyroidism contains a potentiator of lymphocyte mitogenesis, or, alternatively lacks an inhibitor of lymphocyte activation that is present in normal plasma.
Influence of nandrolondecanoate on the pituitary-gonadal axis in males
Authors: Bijlsma J. W. J. , Duursma S. A. , Thijssen J. H. H. , Huber O.
Published: December 2008

Different anabolic steroids can exercise different effects on the pituitary-gonadal axis in males. During a pilot study regarding the possible beneficial effect of the anabolic steroid nandrolondecanoate (ND) on bone metabolism in patients with rheumatoid arthritis additional endocrinological parameters were studied. A significant decrease was found in the serum levels of testosterone, androstenedione and FSH and the ratio of testosterone/oestradiol. There was a significant increase in the serum levels of oestrone. The levels of oestradiol, SHBG, LH and cortisol remained unchanged.

An inhibitory effect of ND on testicular testosterone secretion is assumed. The decrease in androstenedione levels is explained by the diminished testosterone secretion. The rise in oestrone levels is explained by peripheral aromatizing of ND to oestrogens. The presented findings are in accordance with the hypothesis that sex steroids can act directly on the pituitary resulting in selective FSH and LH secretion. The possible role of the ratio testosterone/oestradiol in controlling gonadotrophin output is discussed.
Metabolic studies in women with previous gestational diabetes during contraceptive treatment: effects on serum lipids and high density lipoproteins
Authors: Rådberg Thomas , Gustafson Anders , Skryten Asbjörn , Karlsson Kirsten
Published: December 2008

Triglycerides, cholesterol and phospholipids in serum and high density lipoproteins (HDL) were assessed in 11 women with previous gestational diabetes before and repeatedly during 6 months of low dose progestogen (lynoestrenol = LYN) contraceptive administration. Eight of these women also were followed in an identical manner during non-hormonal contraception (IUD) and 6 of them during combined oral contraceptive administration (EE + LYN).

During the use of IUD or LYN administration neither serum nor HDL lipids changed. The combined OC, EE + LYN, increased serum triglycerides progressively: 73% (P<0.01) after 6 months concomitant with a 100%-increment of HDL triglycerides (P< 0.01). HDL-cholesterol and -phospholipids were not consistently changed. The EE + LYN induced alterations differed from the effects of LYN alone (P< 0.01).

These results suggest that low dose progestogens, such as LYN, could be considered as contraceptive alternatives in women with gestational diabetes. However, combined OC should be avoided in these patients. The present findings differ from those obtained in insulin-dependent diabetics and suggest that a diabetic prediposition enhances the effects of synthetic oestrogens and/or diminishes some of the effects of progestogens on lipid metabolism.
Microautoradiographic studies on distribution of 5α-dihydrotestosterone, cyproterone acetate and oestradiol-17β in human prostatic hyperplasia tissue transplanted to juvenile rats
Authors: Ruberg I. , Senge Th. , Neumann F.
Published: December 2008

While maintaining the actual conditions prevailing in benign prostatic hyperplasia (BPH) in man, transplantation of BPH tissue to newborn rats proved a suitable model for examining the distribution of sexual hormones in different tissue compartments of BPH. In combination with the microautoradiographic method, it was possible to demonstrate the residence of the radioactive androgen 5α-dihydrotestosterone (5α-DHT), the antiandrogen cyproterone acetate (CA) and the oestrogen oestradiol-17β (E2) in the epithelium and/or stroma of human BPH tissue. Quantitative evaluation in the form of a point per area count on photographic pictures yielded a silver grain distribution ratio in epithelium and stroma of 1.3:1 and 1.5:1 for epithelium to stroma after administration of [3H]5α-DHT and [3H]CA administration respectively and 0.5:1 after [3H]E2.

The high tracer recovery rate throughout the stroma following E2 administration supports the current view that the stromal proliferation is attributable mainly to oestrogen influences.

The relatively high silver particle proportion throughout the stroma following 5α-DHT administration corroborates recent findings which suggest that the exclusive androgen dependency of the glandular epithelium can only be considered in conjunction with an active metabolization of androgens in the stroma.

The correspondence in the distribution of the radioactive tracer after [3H]5α-DHT and [3H]CA administration both in the epithelium and stroma suggests that an antagonism may also exist in the stroma.
Effects of a dopamine antagonist (metoclopramide) on the release of the adenohypophyseal hormones in amenorrhoeic patients with and without hyperprolactinaemia
Authors: Seki Katsuyoshi , Uesato Tadashi , Kato Koichi
Published: December 2008

To obtain further insight into the role of endogenous dopamine (DA) on the adenohypophyseal hormones release in amenorrhoeic women, responses of the adenohypophyseal hormones to a DA antagonist, metoclopramide (MCP), were evaluated in 4 normal women, in 9 normoprolactinaemic-amenorrhoeic patients, and in 7 hyperprolactinaemic-amenorrhoeic patients. The hyperprolactinaemic-amenorrhoeic patients were, in the majority, without a demonstrable micro-adenoma. Maximal net increase of prolactin (Prl) after MCP administration were lower (P < 0.01) in hyperprolactinaemic patients compared with those seen in normal women or in normoprolactinaemic-amenorrhoeic patients. Administration of MCP resulted in significant elevation in serum FSH, LH and TSH in hyperprolactinaemic patients, but neither in normal women nor in normoprolactinaemic-amenorrhoeic patients. These findings suggest an increased dopaminergic inhibition of the release of TSH as well as FSH and LH in hyperprolactinaemic-amenorrhoeic patients.
Benserazide and nomifensine in the diagnosis of prolactin-secreting pituitary adenomas
Authors: Pontiroli A. E. , Loda G. , Roggia A. , Scagliola P. , Falsetti L.
Published: December 2008

Benserazide, an inhibitor of dopa-decarboxylase, stimulates prolactin (Prl) release in normal women and in puerperae; nomifensine, a dopaminergic drug able to release dopamine and to inhibit its re-uptake at the post-synaptic level, inhibits Prl release in the same subjects. Similar modifications of Prl release are evident in selected cases of non-tumoural hyperprolactinaemia, while neither drug modifies Prl release in patients with a Prl-secreting pituitary adenoma. The aim of our study was to compare the effect of these drugs in patients with a Prl-secreting pituitary adenoma, in patients with 'functional' hyperprolactinaemia and in patients with minor abnormalities of sellar tomography. Neither drug modified Prl release in patients with macro- or microadenomas; several patients in the remaining groups failed to respond to one or both tests, the concordance between the two tests averaging 75%. Patients responding to both tests, to one test or to neither test showed progressively higher basal Prl levels.

Since benserazide and nomifensine can indicate the presence of a pituitary adenoma earlier than sellar tomography, our results indicate that patients with no Prl response to one or to both tests probably harbour a pituitary adenoma which cannot yet be revealed by sellar tomography.
Thyrotrophin-binding-inhibition assay: comparison of crude and purified membrane preparations
Authors: Garcia Angeles A. , Hunter Anthony N. , Wilkins John A. , von Westarp Christian
Published: December 2008

Two different thyroid membrane preparations (TMP), crude and pure, made from a homogenate of normal human thyroid tissue, were used to test purified serum IgG from 36 patients with Graves' disease, and 10 normal control subjects, in the thyrotrophin-binding-inhibition (TBI) assay. All reagents for the assay were identical, and aliquots of each IgG were tested in both TMP simultaneously, under exactly comparable conditions. Blood was drawn while the patients were hyperthyroid (19), euthyroid (13), or hypothyroid (4); 15 of the patients were untreated and 21 were being treated. The frequency of positive TBI was similar in both TMPs and highest among the 131I-treated patients. Comparison of TBI results in both TMP for each IgG sample revealed wide differences, and 47.1% of the Graves' IgGs were TBI positive in one membrane preparation, while negative in the other. There was no correlation of TBI values between the two TMP, or with clinical status, or the presence of standard thyroid antibodies.

The findings indicate that the IgGs of Graves' disease, as now tested in the TBI assay, bind heterogeneous to different fractions of the thyroid membranes.
Testicular receptors of human chorionic gonadotrophin in adult men. Binding and degradation of the hormone
Authors: Grizard Geneviève , Boucher Daniel , Hermabessière Jean , Grizard Jean
Published: December 2008

Binding and degradation of human chorionic gonadotrophin (hCG) to testicular tissue obtained by biopsy from 9 men with gonadal disorders were investigated. Vacant hCG receptors were assayed in partially purified testicular homogenates using [125I]hCG (radio-iodinated with chloramine T). Degradation of [125I]hCG during exposure to human testicular preparations was measured in terms of the ability of supernatants to specifically bind to rat testicular receptors.

Binding of [125I]hCG was time and temperature dependent. At 37°C, a maximum was reached at 8 h. It was also found to be a saturable process with respect to homogenate and hormone concentrations. Association constants and number of binding sites determined in 9 men, using Scatchard plot and saturation curve analysis ranged, respectively, from 0.2 to 1.8 × 1010m−1 and from 92 to 3427 fmol/g testis or 7 to 380 fmol/mg protein. Degradation of [125I]hCG increased with temperature and time of exposure to human testicular homogenate. It increased also with increasing human testicular homogenate concentration and substrate concentrations. For a similar concentration of [125I]hCG, per cent of degraded hormone ranged from 32 to 57, according to the subjects. These results show that human testicular homogenates are capable of binding and degrading hCG in vitro. Biological and physiological implications of degradation for hormone binding are discussed.
Ontogeny of thyroid peroxidase activity in perinatal rats
Authors: Fukiishi Y. , Harauchi T. , Yoshizaki T. , Hasegawa Y. , Eguchi Y.
Published: December 2008

The ontogeny of thyroid peroxidase (TPO) activity was investigated in rat foetuses and neonates. From day 19 to 22 of gestation in intact pregnant rats, the TPO activity in their foetuses increased with foetal age.

Following maternal treatment with propylthiouracil (PTU), the TPO activity markedly increased in foetuses on and after day 20 of gestation. The TPO activity in encephalectomized foetuses increased as markedly as that in intact littermates, whereas that in hypophysectomized littermates failed to increase.

Newborn rats nursed by mothers treated with PTU had a TPO activity similar to that in controls of untreated mothers. There was also no difference in the TPO activity between hypophysectomized adult females and intact adult ones.

These observations show that in foetal rats, TPO activity increases disproportionately to the thyroid weight, but not in newborn and adult rats, and suggest that preferential synthesis of this enzyme occurs in addition to cell hypertrophy during foetal life.
Developmental patterns of levels of corticosterone and of corticosterone binding in the serum of female rats: effects of ovariectomy and adrenalectomy
Authors: Vallette G. , Delorme J. , Benassayag C. , Savu L. , Nunez E. A. , Meijs-Roelofs H. M. A. , Kramer P.
Published: December 2008

Corticosterone concentrations and corticosterone binding in the serum were studied in immature female rats, using radioimmunoassay and batchwise gel equilibration techniques. A parallel developmental pattern was found for corticosterone levels and its serum binding with a neonatal drop, followed by low levels until 12 days of age and a rise between 12 and 28 days of age.

Effects of adrenalectomy, of ovariectomy, of the combined operation and of sham-operations, performed at various ages, were also studied. Adrenalectomy performed at 5 days of age did not decrease serum corticosterone concentrations within a 6-day period whereas it did in older rats. Complete disappearance of corticosterone from the blood occurred only in adult rats after combined adrenalectomy/ovariectomy.

Ovariectomy and sham-operations in the younger age groups (5–15 days) caused a gradual increase in corticosterone concentration with maximal values 6 days after operation or later. The response of corticosterone secretion to these operations became more moderate and quicker, i.e. more adult-like, at 28 days of age, the age where corticosterone concentrations in intact rats also seemed to reach a plateau at an adult-like level.

Corticosterone binding changed only marginally after ovariectomy or sham-operations until 28 days of age, when an increase was induced by these operations. After adrenalectomy or combined adrenalectomy/ovariectomy, however, marked increases in serum binding of corticosterone were always seen. In summary: though a parallel developmental pattern of serum corticosterone levels and corticosterone binding was seen in the maturing rat, interference with the normal condition causes divergent responses in these two parameters. Moreover, the responses vary with maturational age.
Prolactin in the circulation of chronically catheterised piglet foetuses and pregnant sows, and the effect of thyrotrophin-releasing hormone
Authors: Macdonald Alastair A. , Bevers Mart M. , Ellendorff Franz , Taverne Marcel
Published: December 2008

We chronically catheterised 12 piglet foetuses and 11 sows to determine the changes in circulating concentrations of prolactin during the last 2 weeks of gestation. Prolactin levels were measured by homologous radioimmunoassay and were found to average 2.12 ± 0.23 ng · ml−1 in the foetuses and 4.19 ± 0.84 ng · ml−1 in the sows. Foetal concentrations of prolactin increased significantly during the time period of the study. There was no change in maternal concentrations over the corresponding time. Injection of 5 μg TRH into 7 foetuses increased the plasma concentrations of prolactin in 6 animals, produced no apparent change in the seventh foetus and did not affect maternal concentrations of prolactin. The magnitude of the maximum response to TRH of the younger foetuses (< 107 days Δ = 0.7, 1.3, 4.2 ng · ml−1) was substantially less than that of the foetuses prior to term (> 107 days Δ = 6.4, 21.7, 27.5 ng · ml−1). Injection of saline and the haemorrhage of blood sampling produced no significant change in the initial concentration of prolactin. We conclude that prolactin is present in the circulation of the pig foetus, that it is produced endogenously in lower concentrations than in the pregnant sow and that the foetal responsiveness to TRH stimulation increases towards the end of gestation.
Hormonal and metabolic effects of intravenous infusion of prostacyclin in healthy women
Authors: Ylikorkala Olavi , Knip Mikael , Mäkäräinen Leo , Pakarinen Arto , Viinikka Lasse
Published: December 2008

To study the hormonal and metabolic effects of prostacyclin (PGI2), 6 healthy women were infused iv with PGI2 (1, 2, 4, and 8 ng/kg/min, each for 20 min) dissolved in glycine buffer, or with glycine buffer only. Serial blood samples collected before, during and after the infusion were assayed for FSH, LH, prolactin, growth hormone, thyrotrophin, oestradiol, progesterone, testosterone, cortisol, thyroxine, triiodothyronine, renin, aldosterone, glucose, insulin, glucagon, cholesterol, high density lipoprotein-cholesterol, triglycerides, alkaline phosphatase, alanine and aspartate aminotransferases, bilirubin, sodium, potassium, chloride, calcium, inorganic phosphorous, creatinine and uric acid. PGI2 infusions were accompanied by increased levels of prolactin, growth hormone and cortisol, probably due to the stressful side-effects during PGI2 infusion. In addition, plasma renin activity, glucagon and blood glucose increased, whereas the other variables measured did not change. These PGI2-effects should be kept in mind, when PGI2 is used in clinical practice.
Independence of the androgen-induced mRNA synthesis on exogenous glucose in the ventral prostate of the rat
Authors: Kuosa Anja
Published: December 2008

Poly (A)-containing RNA species were isolated from prostatic polysomes after administration of testosterone to castrated rats. After exposure of prostatic tissue to radiolabelled uridine in vitro for 1 h the radioactivity of polysomal poly (A)-RNA increased at 6–12 h after testosterone treatment, which coincides with the hormonal activation of protein synthesis under the same experimental conditions. The increased radioactivity of polysomal mRNA was not due to changes in the uptake and phosphorylation or radiolabelled uridine or in the endogenous content of uridine nucleotides representing thus an increased mRNA content.

Electrophoretic patterns of double-labelled polysomal mRNA failed to show detectable amounts of androgenspecific species. The larger part of increase in mRNA content thus consists of mRNAs common to prostatic cells of both testosterone-treated and non-treated castrated animals.

The hormonal stimulation of polysomal poly (A)-RNA accumulation was not dependent upon exogenous glucose which is in contrast to protein synthesis. However, glucose was necessary for the hormonal activation of the phosphorylation of [3H]uridine leading ultimately to increased labelling of all RNA species. It is concluded that increased accumulation of polysomal mRNA may be necessary, but not sufficient for the hormonal activation of protein synthesis.
Ultrastructural characterization of human corticotrophs (ACTH cells)
Authors: Tsumuraya Masaru , Kameya Toru
Published: December 2008

Ultrastructural characterization of human corticotrophs (ACTH cells) was performed by 'superimposition technique', which enabled detailed ultrastructural observation of immunoreactive ACTH cells in adjacent semi-thin light microscopic immunoperoxidase and routine electron microscopic sections. The human corticotrophs were large and round or polygonal and were not stellate. They had scanty rough endoplasmic membranes and were packed with numerous large secretory granules measuring from 250 to 500 nm in diameter. The sizes of secretory granules in 6 human pituitaries were 448 ± 128, 344 ± 86, 448 ± 117, 244 ± 65, 316 ± 76, and 340 ± 93 nm, respectively. The granules were not seen in a single row along the plasma membrane as is the case in the rat. They possessed somewhat irregular outlines with a rarely discernible halo. Different densities of granule matrices were occasionally found. The cells often contained a few large heterogeneous vacuoles. From these findings, the human ACTH cells were recognized to be remarkably different in cell shape and size, properties of secretory granules and cytoplamic inclusions from those of the rat pituitary gland. In respect to secretory granule properties, the human ACTH cells are similar to those of some other mammals (fox, young pig, and lerot). More data is required to elucidate the relationship between human ACTH cell morphology and functional state.
Episodic secretion of vasopressin in man
Authors: Hammer M. , Engell H. C.
Published: December 2008

The plasma arginine vasopressin concentration (pAVP) was measured in blood samples obtained from an internal jugular vein of 8 patients who under-went surgery for a carotid artery stenosis. Ten blood samples were taken with 1 min interval during the operation. Arterial pAVP was measured in 10 simultaneous samples from a radial artery and the brain veno-arterial difference of pAVP was calculated. The veno-arterial difference was 0–3 pg/ml in 7 of the patients, while it increased to 35 pg/ml upon baroreceptor stimulation in one patient. A pulsatile pattern was found in the veno-arterial difference of pAVP both at low and higher peripheral pAVP levels. This appeared to reflect a discontinuous release of AVP from the neurohypophysis. The described method results in a more accurate picture of ongoing secretory activity than can be obtained by measurements of peripheral pAVP alone. The general usefulness of the method, however, is restricted by the need of a multitude of samples and the difficult approach to the internal jugular vein.
Improved radioassay for human antithyroglobulin
Authors: Beall Gildon N. , Parslow Margaret E. , Kruger Sally R. , Zaidi Azra
Published: December 2008

Human antithyroglobulin (anti-HTg) in serum and tissue cultures can be assayed by coprecipitation with 125I-labelled human thyroglobulin (HTg). Coprecipitation of the antibody from different sera gives roughly parallel curves, so that a standard serum can be used for quantitiation of other sera. By assessing the binding of 125I-labelled HTg in antigen excess we estimate the antibody content of the standard serum to be 0.14 ng anti-HTg per ml. Shortened incubation minimizes non-specific binding of HTg to serum globulins and obviates pre-assay absorption of HTg. Radioassay for thyroglobulin antibodies in serum correlated with values obtained by solid-phase competitive-binding assay (SPCB). One unit in our assay corresponds to 0.014 unit by the latter assay and to 0.12 units of MRC Research Standard A. We confirm that serum thyroglobulin seriously interferes with SPCB assay, giving what appears to be positive results for anti-HTg where none is detected with our assay. Values for anti-HTg are depressed by serum HTg but only in the presence of very high concentrations in serum.
Desensitisation of rat thyroid to the growth-stimulating action of TSH during prolonged goitrogen administration Persistence of refractoriness following withdrawal of stimulation
Authors: Wynford-Thomas D. , Stringer B. M. J. , Williams E. D.
Published: December 2008

We have previously shown that administration of goitrogen to the rat leads to a sustained elevation of serum TSH but to only a short-lived burst of mitotic activity in the thyroid, growth eventually ceasing after a few months. This work investigates the possibility that this progressive desensitisation may result simply from continued exposure to high levels of TSH and examines the effect of a period of interruption of goitrogen treatment on the sensitivity of the gland to subsequent TSH stimulation.

Rats were treated with the goitrogen aminotriazole (ATA) for an initial period of 80 days to reach the plateau of thyroid growth. ATA was then withdrawn for 25 days and subsequently re-introduced for a further 35 days. Animals were killed in groups of 8 at frequent intervals and the following measurements carried out: — Serum TSH, T3 and T4, thyroid weight, follicular cell number and mitotic activity.

The initial period of ATA treatment led to a 5-fold increase in serum TSH, a 10-fold increase in thyroid weight and a 9-fold increase in follicular cell number. Mitotic activity stabilised at a few times control levels. Following withdrawal of ATA, TSH and mitotic activity fell to below normal. Thyroid weight fell by 66% but there was no significant fall in follicular cell number. Re-introduction of ATA simply led to a return of all variables to their previous 'stimulated' levels. There was no second burst of mitotic activity and no renewed thyroid growth.

The results show that the desensitisation of follicular cells to the growth-stimulating action of TSH following prolonged stimulation is not reversed by withdrawal of the stimulus, and is therefore unlikely to be mediated by a 'downregulation' at receptor or post-receptor level of the type observed for functional responses in vitro.

Other possible mechanisms are discussed.
Protection by nicotinamide against streptozotocin-induced reduction in pancreatic TRH
Authors: Kazumi Tsutomu , Utsumi Masafumi , Hirose Yoshikazu , Ishihara Kazuhide , Makimura Hiroyuki , Ejiri Kazushige , Taniguchi Hiroshi , Baba Shigeaki
Published: December 2008

The concentration of thyrotrophin-releasing hormone (TRH) immunoreactivity was determined in pancreatic islets and acini in the rat. In addition, timecourse changes in TRH in response to an iv injection of streptozotocin (65 mg/kg body weight) with or without nicotinamide (500 mg/kg body weight) were examined in the whole pancreas. Furthermore, pancreatic TRH was measured in diabetic rats treated with insulin for 3 weeks. The TRH concentration in rat islets was 42-fold higher than in exocrine glands, indicating that the majority of pancreatic TRH is of islet origin. The mean concentration of pancreatic TRH decreased to 60 and 65% of the respective control values at 4 and 7 h after administration of streptozotocin, respectively. At 24 h, it fell to 10% of control values without significant changes in TRH levels in the hypothalamus and gastrointestinal tract. In contrast, no significant change in pancreatic TRH was noted in rats given combined treatment with streptozotocin and nicotinamide. The injection of streptozotocin alone resulted in severe hypoglycaemia at 7 h and hyperglycaemia at 24 h, whereas neither resulted from the combined treatment. Insulin therapy had no influence on the decreased TRH concentrations in the diabetic pancreas. These results suggest that TRH may be localized to the B cells of pancreatic islets, and that the marked reduction in TRH in diabetic pancreases is not a metabolic consequence of insulin deficiency.
Modification by Su-10'603 of the response to histamine on the production of cortisol and corticosterone in isolated canine adrenocortical cells
Authors: Hirose T. , Matsumoto I. , Aikawa T.
Published: December 2008

The effect of Su-10'603 on the cortisol and corticosterone response to histamine in dispersed canine adrenocortical cells was examined. The production of cortisol and corticosterone in isolated dog adrenocortical cell incubations increased in a dose-dependent manner at concentrations of histamine between 0.01 and 10.0 μg/ml medium, with the predominant production of cortisol. When Su-10'603 (0.005 to 5.0 μg/ml medium), an inhibitor of 17α-hydroxylation on corticosteroidogenesis, was added in cell incubations with histamine (1.0 μg/ml medium), the production of cortisol decreased in a reciprocal fashion, with a concomitant increase of corticosterone production. At the concentration between 0.05 and 0.1 μg Su-10'603/ml medium, there was a shift from cortisol to corticosterone as the predominant product. These results indicate that in the dog, histamine at pathophysiological concentration stimulates steroidogenesis and acts at a relatively early stage in the biosynthetic pathway.
Lipoproteins during oral and cutaneous administration of oestradiol-17β to menopausal women
Authors: Fåhraeus Lars , Larsson-Cohn Ulf , Wallentin Lars
Published: December 2008

Thirty-eight post-menopausal women were randomly allocated to substitution treatment with either oestradiol-17β orally (2–4 mg) or cutaneously (3 mg). The concentrations of cholesterol (C), triglycerides (TG) and phospholipids were determined in the high density lipoprotein (HDL)-, the low density lipoprotein (LDL)- and the very low density lipoprotein (VLDL)- fractions twice before medication and after 2, 4 and 6 months of treatment.

Both treatments gave satisfactory clinical results. Oral doses increased the HDL and decreased the LDL thus raising the HDL-C/LDL-C ratio. The higher oral dose also increased the TG concentration. Cutaneous oestradiol gave only minimal changes of the lipoproteins.

The lipoprotein changes observed during treatment with oral oestradiol might reduce the risk for atherosclerotic disease. Therefore, from a lipoprotein point of view, oral oestradiol treatment probably could be considered beneficial. The cutaneous oestradiol treatment had comparable clinical effects without any influence on the lipoprotein pattern.
Relationship of follicle stimulating hormone (FSH)-sensitive adenylate cyclase activity to FSH binding in immature rat ovaries following administration of pregnant mare serum gonadotrophin
Authors: Lee C. Y. , Reichert L. E.
Published: December 2008

The time and dose-response relationships of human follicle stimulating hormone (hFSH)-sensitive adenylate cyclase activity to hFSH binding was studied in the immature rat ovary following an sc injection of pregnant mare serum gonadotrophin (PMSG). When an optimal dose of PMSG (10 IU/rat) was administered, a marked increase in hFSH-sensitive activity was observed at day 2, followed by a sharp decline at day 3. This was accompanied by a parallel rise and fall in ovarian hFSH binding activity. When immature rats were given various doses (5–100 IU/rat) of PMSG for 2 days, hFSH-sensitive adenylate cyclase activity increased sharply and maximal stimulation was obtained at 10 IU/rat. A close correlation was also observed with respect to dose-response for hCG-sensitive adenylate cyclase and hCG binding activities. It is concluded that: 1) PMSG administration with an optimal dose to the immature rat induced ovarian FSH and LH-hCG receptors, and an adenylate cyclase system highly sensitive to hFSH and hCG, and 2) the acquisition and responsiveness of adenylate cylcase to gonadotrophins are closely related to the appearance and the numbers of gonadotrophin receptors.
Long-term treatment of osteoporosis with 24,25 dihydroxycholecalciferol
Authors: Reeve J. , Tellez M. , Green J. R. , Hesp R. , Elsasser U. , Wootton R. , Hulme P. , Williams D. , Kanis J. A. , Russell R. G. G. , Mawer E. B. , Meunier P. J.
Published: December 2008

Five patients with involutional osteoporosis were treated with 24,25 dihydroxycholecalciferol (24,25-(OH)2D3) for 6 months, in doses sufficient to double plasma levels at that time. Dietary calcium absorption transiently improved by nearly 2 mmol Ca per day at 2 weeks, but this effect was lost by 6 months. The calcium and phosphate balances followed the trends in calcium absorption. Only twenty-five dihydroxyvitamin D levels changed little. Histomorphometric and kinetic indices of new bone formation and bone blood flow remained stable but there was an increase in urine hydroxyproline at 6 months, which was of borderline statistical significance. Treatment at this dosage of 24,25(OH)2D3, which increased plasma levels within the physiological range, conferred no measurable long-term benefit on our patients. Larger doses, or combination therapy, may warrant further clinical evaluation in osteoporosis.
The possible prognostic value of serum prolactin increment during pregnancy in hyperprolactinaemic patients
Authors: Andersen A. Nyboe , Starup J. , Tabor Ann , Jensen H. Kålund , Westergaard j. G.
Published: December 2008

In 15 hyperprolactinaemic, infertile patients achieving 17 bromocriptine-induced pregnancies, the presence or absence of prolactin (Prl) increment in the 3rd trimester of pregnancy was correlated to the basal Prl levels before treatment and after pregnancy. The hyperprolactinaemic patients revealed a marked heterogeneity in the Prl increment compared to normal women. Five patients showed a pronounced increase in serum Prl during gestation, whereas Prl levels were unaltered or decreased slightly in 10 patients. In the latter group of patients serum Prl was significantly (P<0.01) lower after pregnancy than before treatment.

Our study indicates that some hyperprolactinaemic patients may benefit from a pregnancy, and that these patients probably can be identified, as they do not show any significant changes in Prl levels during pregnancy.
Human growth hormone blunts Na2EDTA-induced hypocalcaemia in hyposomatotrophic children
Authors: Root Allen W. , Duckett Gregory E. , Sweetland Margaret , Livingston Catherine , Reiter Edward O.
Published: December 2008

An infusion of disodium ethylenediamine tetraacetate (Na2EDTA) (0.13 mmol/kg for 2 h) was administered to 10 hyposomatotrophic children prior to and after 6 and 12 months of treatment with human growth hormone (hGH). Total and ionized calcium and immunoreactive parathyroid hormone (iPTH) concentrations were determined. Mean basal total and ionized calcium concentrations did not change during the year of treatment with hGH. The nadir concentrations of total and ionized calcium increased progressively during hGH administration and after 12 months were significantly increased over pre-treatment values (total calcium: pre-treatment 1.85 ± 0.32 (sd) mmol/l, + 12 months 2.10 ± 0.15, P < 0.01; ionized calcium: pre-treatment 0.55 ± 0.31 mmol/l, + 12 months 0.78 ± 0.14, P < 0.05). The mean basal concentration of iPTH increased slightly after 12 months of hGH administration (pre-treatment 72 ± 18 pg/ml, + 12 months 106 ± 71, P < 0.05), but Na2EDTA-evoked secretion of iPTH was not significant altered by hGH.
Interaction of gastric inhibitory polypeptide (GIP) and cholecystokinin (CCK-8) with basal and stimulated insulin secretion in mice
Authors: Ahrén Bo , Hedner Pavo , Lundquist Ingmar
Published: December 2008

The interaction of GIP and CCK-8 with basal insulin secretion and with insulin release induced by glucose or by the β-adrenoceptor agonist l-isopropylnoradrenaline (l-IPNA) was studied in mice.

GIP and CCK-8, when injected in threshold doses not affecting basal insulin secretion, did markedly enhance basal insulin release when given simultaneously. Maximal doses of the two peptides, on the other hand, did not potentiate each other's action, but displayed a pure additive effect on insulin secretion.

Insulin release induced by a half-maximal dose of glucose was slightly potentiated by the threshold dose of GIP and markedly potentiated by the maximal dose i.e. the effect was greater than the algebraic sum of the individual actions. CCK-8 was without potentiating effect at both dose levels. The combination of GIP and CCK-8 did not display the potentiating effect of GIP alone on glucose-stimulated insulin release. However, an additive action was observed at both dose levels.

Insulin release stimulated by a half-maximal dose of l-IPNA was not affected by either GIP or CCK-8 at the threshold doses. The combination of the two peptides and l-IPNA, however, displayed a lower response than that expected from an additive effect. Similarly, at the high dose level of the peptides, the combination of GIP plus CCK-8 and l-IPNA as well as CCK-8 alone plus l-IPNA displayed a lower insulin response than that expected from an additive effect. GIP alone plus l-IPNA gave the expected additive effect.

The results show that interactions between different gastrointestinal polypeptides with insulin release may greatly change the expected effect exerted by any individually tested peptide, and that the action of the peptides on stimulated insulin secretion is highly dependent on the nature of the secretagogue. Such complex interactions must be borne in mind in the search for the incretin factor(s).
Effects of various replacement oestrogens on hepatic transcortin synthesis in climacteric women
Authors: Schwartz Ulf , Volger Heide , Schneller Eberhard , Moltz Lothar , Hammerstein Jürgen
Published: December 2008

The influence of peri-menopausal oestrogen replacement therapy upon protein synthesis in the liver was investigated. Changes in the cortisol-binding capacity of transcortin (TC-BC) were utilized as an indicator of hepatic oestrogen sensitivity. Forty-two climacteric women were studied before and after treatment with various drugs at different doses (patients receiving identical compounds served as their own controls for the evaluation of dosage effects; duration of medication: 14 days at each dose). Oral administration of oestriol (1 and 2 mg daily; n = 6), oestriol (1 and 2 mg daily) + oestradiol-17β (2 and 4 mg daily; n = 8), oestradiol valerate (1, 2, 4 and 6 mg daily; n = 6), conjugated equine oestrogens (0.3 and 0.6 mg daily; n = 6), sodium oestrone sulphate (0.8 and 1.6 mg daily) + sodium equilin sulphate (0.2 and 0.4 mg daily; n = 6) and quinoestrol (25 μg daily; n = 6) failed to alter TC-BC. However, ingestion of higher doses of conjugated equine oestrogens (0.9 and 1.25 mg daily; n = 5) and quinoestrol (50 μg daily; n = 6) caused a significant rise (P < 0.01). Ethinyloestradiol was given orally as a reference substance and elicited an elevation of expected magnitude. Vaginal administration of dienoestrol cream (1 mg daily; n = 4) did not change TC-BC. These data indicate that the hepatotrophic effects of replacement oestrogens vary depending on the preparation and dosage selected for treatment.
Is the adrenal angiotensin receptor angiotensin II — or angiotensin III like?
Authors: Braley Lynne M. , Menachery Alphonsa I. , Underwood Richard H. , Williams Gordon H.
Published: December 2008

In order to determine whether the adrenal receptor is primarily directed at angiotensin II (All) or angiotensin III (AIII) the following in vitro experiments were performed examining aldosterone responsiveness in isolated glomerulosa cells. 1) Cells exposed to increasing doses (2.4 × 10−10 m – 2.4 × 10−6 m) of All or AIII were found to be significantly more responsive to All (All's ED50 was 6.3 × 10−10 m vs AIII's 4.6 × 10−9m P < 0.001). 2) Octapeptide analogues (Sar1 Ala8 and Asn1 Ala8), while demonstrating different inhibitory potencies relative to each other, were equally effective in blocking All vs AIII stimulation. 3) The heptapeptide analogues (des1 Ala8 and des1 Ile8) however, inhibited AIII stimulation preferentially (P < 0.01). 4) The 8 alanine octapeptide analogues were better inhibitors of both All and AIII stimulation than the 8 alanine heptapeptide analogue. 5) HPLC analysis indicated that All and AIII were being degraded at the same rate during the incubation procedure.

These results, taken together, strongly suggest that the angiotensin adrenal receptor is an All receptor.
Basal and TRH stimulated serum levels of TSH in patients with hyperprolactinaemia and in subjects on oestrogen treatment
Authors: Erfurth Eva M. , Hedner Pavo , Nilsson Anders
Published: December 2008

In 21 hyperprolactinaemic patients without other signs of pituitary dysfunction the mean basal serum level of TSH was 4.4 ± 0.47 μU/ml that was significantly (P < 0.001) higher than controls (2.5 ± 0.16 μU/ml and oestrogen treated individuals (2.4 ± 0.29 μU/ml). The TSH increase was more pronounced (P < 0.05) in hyperprolactinaemic patients without sellar enlargement and with moderately elevated plasma prolactin levels (155 ± 42 μg/ml) than in patients with sellar enlargement and higher plasma prolactin levels (857 ± 306 μg/ml). The serum levels of thyroxine and triiodothyronine in the hyperprolactinaemic patients did not differ significantly from controls. Patients with thyroid antibodies were excluded. The increased basal serum level of TSH in hyperprolactinaemia is compatible with the concept of a reduced dopaminergic tonus as the mechanism for both changes. In patients with advanced hyperprolactinaemia and sellar enlargement the high prolactin level may induce some inhibition of TSH release and explain their lower basal serum level of TSH that was probably not due to pituitary compression as they responded normally to TRH.

The TSH response to TRH was significantly (P < 0.05) correlated to the basal serum TSH in all groups. The regression lines were very similar for hyperprolactinaemic patients and controls suggesting that in hyperprolactinaemia the thyrotroph has not changed its mode of response to TRH. In contrast, oestrogen treated subjects in addition to dependence on basal serum TSH levels showed a genuinely augmented response to TRH (164.6 ± 20.3%, P < 0.01) compared to controls.
Oestrogens induce an LH surge in a prepubertal patient with 45,X gonadal dysgenesis under prolonged pulsatile LRH administration
Authors: Delemarre-van de Waal Henriette A. , Van den Brande J. L. , van Kessel H. , Schoemaker J.
Published: December 2008

A nine year old prepubertal patient with 45,X gonadal dysgenesis received pulsatile LRH administration for 3 weeks, every 90 min 10 μg iv. In the first week LH and FSH levels increased from prepubertal levels into the castrate range. Under 2.5 μg ethinyloestradiol (EE) LH levelled off for 3 days, followed by an LH surge. FSH showed an ethinyloestradiol dose-dependent decrease. These data suggest that: 1) pulsatile LRH administration may help to distinguish prepubertally those Turner patients with potential ovarian function from those without; 2) oestrogens exert both a negative and positive feedback action at the pituitary level in the LRH treated human; 3) the pituitary does not need 'pubertal maturation' for developing positive feedback to oestrogens. This supports the notion that pubertal maturation is confined to suprapituitary changes.
Effects of capture and venipuncture on serum levels of prolactin, growth hormone and cortisol in outdoor compound-housed female rhesus monkeys (Macaca mulatta)
Authors: Blank Michael S. , Gordon Thomas P. , Wilson Mark E.
Published: December 2008

The effects of capture and repeated venipuncture on serum levels of prolactin (Prl), growth hormone (GH) and cortisol (F) were assessed in outdoor, open compound-housed, socially-living female rhesus monkeys. In animals unaccustomed to capture, blood samples obtained soon after capture (time zero) contained relatively high concentrations of both Prl and GH (Prl>30 ng/ml, GH> 10 ng/ml) which declined dramatically over the next 60 min. Mean levels of serum Prl in capture-naive lactators (n=6) and non-lactators (n=5) were 83 ± 28 (sem) and 32 ± 11 ng/ml at time zero and fell significantly (P < 0.01) within 60 min to 28 ± 10 and 6 ± 2 ng/ml, respectively. GH levels in serum also decreased over time and the time-dependent reductions in serum Prl and GH were unaffected by intervening venipuncture or caging. In contrast, serum F rose after capture reaching peak values (330 – 515 ng/ml) 60 min later. The delayed rise in serum F could reflect the time required for pituitary trophic stimulation of the adrenals after capture. Capture-acclimated, lactating females displayed lower levels of Prl at time zero with values approximating those found at 90 min in the capture-naive group. Furthermore, capture-acclimated pregnant animals exhibited a significant rise in Prl levels after parturition in the spring. These studies suggest a non-specific, capture-related release of pituitary hormones in capture-naive, compound-housed female rhesus. However, animals that have been captured and bled repeatedly over some weeks or months show lower, physiological levels of Prl, indicating an acclimation to the procedure. Thus, outdoor-housed rhesus monkeys which have been acclimated to capture can be a useful model for studying the involvement of Prl in reproduction in this species.
Dopaminergic regulation of 18-hydroxycorticosterone and aldosterone secretion in man
Authors: Sowers James R. , Beck Frances W. J.
Published: December 2008

This study was designed to investigate dopaminergic mechanisms involved in the control of corticosteroid secretion. Plasma renin activity (PRA), prolactin, cortisol, corticosterone, 11-deoxycorticosterone, 18-hydroxycorticosterone (18-OHB) and aldosterone responses to metoclopramide 10 mg iv in the presence of a vehicle or dopamine (3 μg/kg/min) infusions, or domperidone 10 mg iv were evaluated in 10 normal males. Metoclopramide, and the peripheral dopamine antagonist, domperidone both resulted in rises in serum prolactin levels. Metoclopramide, but not domperidone, resulted in parallel rises in plasma 18-OHB and aldosterone levels. Dopamine infusion markedly inhibited prolactin, 18-OHB and aldosterone responses to the central and peripheral dopamine antagonist metoclopramide. Administration of the dopamine agonist, bromocriptine, 2.5 mg three times a day for 4 days suppressed (P < 0.01) mean 24 h plasma 18-OHB levels from 22.1 ± 2.1 to 15.8 ± 1.5 ng/dl. These results suggest that dopaminergic mechanisms modulate the secretion of 18-OHB and aldosterone. The circadian rhythm of 18-OHB secretion is not dependent on dopaminergic mechanisms.
Effect of sulpiride-induced hyperprolactinaemia on catecholamine turnover and LRH concentration in the medial basal hypothalamus of rats
Authors: Chatani Fumio , Aono Toshihiro , Koike Koji , Tasaka Keiichi , Kurachi Keiichi
Published: December 2008

In order to clarify the mechanism of hyperprolactinaemic anovulation, the medial basal hypothalamic (MBH) catecholamine (CA) turnover and LRH concentration, and the serum levels and pituitary contents of gonadotrophins and prolactin (Prl) in hyperprolactinaemic female rats were examined. Hyperprolactinaemia (HPrl) was produced by oral administration of sulpiride for 10 consecutive days; each measurement made on the sulpiride-treated rats was compared with that of control dioestrus rats. Prl, LH, FSH and LRH were determined by radioimmunoassay; CA turnover, as assessed by the accumulation of CA following monoamine oxidase inhibition, was assayed by high performance liquid chromatography with electrochemical detection. Sulpiride treatment induced (1) an increase in the serum Prl and a decrease in the serum LH, (2) an increase in the pituitary FSH and LH contents, (3) an increase in the MBH LRH concentration, and (4) an increase in the MBH dopamine (DA) turnover. These results suggest that HPrl may induce anovulation by impaired LH secretion which was caused by the suppression of LRH release due to an increase in DA turnover in the MBH.