Showing papers in "European Journal of Endocrinology in 1985"

Comparison of in vivo effects of insulin-like growth factors I and II and of growth hormone in hypophysectomized rats.

Abstract: Pure human IGF I (43 and 103 micrograms/day) and IGF II (131 micrograms/day) were infused into hypophysectomized rats during 6 days by means of sc implanted minipumps. Their effects on several growth indices were compared with those of various doses of sc infused human growth hormone. Growth hormone infusion produced a dose-dependent rise of endogenous rat IGF from 39 (without growth hormone) to 86 microU equivalents/ml (with 400 mU hGH/day) as determined by a competitive protein binding assay with a human IGF standard. In rats receiving the two doses of IGF I, total serum IGF levels rose to 83 and 99 microU equivalents/ml, respectively, in those receiving the IGF II dose the total serum IGF level rose to 146 microU equivalents/ml. These increases corresponded to steady state levels of 168 and 286 ng/ml of immunoreactive insulin-like growth factor (IR-IGF) I and 320 ng/ml of IR-IGF II. IGF I, but not IGF II led to an increase in body weight similar to that induced by the low doses of hGH (12.5 and 25 mU, respectively). The rise of endogenous rat IGF as well as the infused human IGF I and II caused a widening of the tibial epiphysis and an increase of the [3H]thymidine incorporation into costal cartilage. With respect to these two indices IGF II was clearly less potent that IGF I. When expressed in microU equivalents of the protein binding assay, endogenous rat IGF induced by hGH appeared to be relatively more effective than infused human IGF I or II.(ABSTRACT TRUNCATED AT 250 WORDS)

Thyroid carcinoma and thyroiditis in an endemic goitre region before and after iodine prophylaxis

Abstract: Iodine prophylaxis was introduced to the moderately severe goitre endemic area in Salta, Argentina, in 1963. All thyroidectomies from a 20 year period were reviewed, and 148 thyroid malignancies carefully studied. The period from 5 to 15 years after iodization was associated with a lower frequency of follicular carcinomas and a higher frequency of papillary carcinomas than the period before and up to 5 years after prophylaxis. Lymphoid infiltration in the non-tumorous thyroid was relatively infrequent before iodine prophylaxis: it was much higher in each of the post-prophylaxis periods. These results, in agreement with other studies, support the view that an increased iodine intake is associated with an increased incidence of papillary carcinoma of the thyroid and thyroiditis.

Insulin-like growth factors (IGF) 1 and 2 in human foetal plasma and relationship to gestational age and foetal size during midpregnancy.

Abstract: IGF-1 and IGF-2 were measured by specific radioimmunoassay after acid-ethanol extraction of plasma obtained by foetoscopy from 20 normal foetuses aged 15-23 weeks. IGF-1 and IGF-2 levels were 36 +/- 11 and 162 +/- 55 ng/ml, respectively. In comparison, levels in cord blood were 84 +/- 58 and 264 +/- 176 ng/ml, respectively, and in adult plasma were 410 +/- 106 and 818 +/- 272 ng/ml. Both IGF-1 and IGF-2 were in the normal foetal range in a further three foetuses with anencephaly and two foetuses with spina bifida. No sex difference was observed. IGF-1 was positively correlated with foetal body weight (P less than 0.001), placenta weight (P less than 0.02) and with body length measured crown-rump (P less than 0.01) or crown-heel (P less than 0.02). No correlation between IGF-2 and body weight, length, placenta weight or gestational age was found. Both IGF-1 and IGF-2 are present in the human foetal circulation earlier in gestation than has previously been demonstrated, the levels being low throughout this period of gestation in comparison with adult plasma.

Identification of insulin-like growth factor-I and its receptors in the rat testis.

Abstract: As part of a study of the testicular production and action of insulin-like growth factor-I (IGF-I), adult rat testes were extracted with acidified methanol, yielding an immunoreactive IGF-I fraction corresponding in size to human IGF-I. The mean IGF-I content (+/- SEM) of testes weighing approximately 1.1 g was 51.5 +/- 5.6 ng/testis, and was not due to serum contamination. After a 3-day fast testicular IGF-I decreased by 80%, whereas serum IGF-I levels declined by 90%. Testicular homogenates and isolated Leydig cells were shown to contain specific IGF-I receptors, Ka = 2 X 10(9) M-1, with 10% IGF-II cross-reactivity. The concentration of these receptors was 2 pmol binding sites per testis, or 3.3 fmol per 10(6) Leydig cells. However IGF-I at 250 ng/ml had no effect on basal or hCG-stimulated testosterone production by isolated Leydig cells, measured over 3 h. Although an effect of IGF-I over longer incubation periods cannot be excluded, it is also possible that testicular IGF-I has a mitogenic role, rather than acting on differentiated testicular functions.

A somatostatin analogue inhibits chondrosarcoma and insulinoma tumour growth

Abstract: The in vivo effects on tumour growth of a potent somatostatin analogue, SMS 201-995 [H-(D)Phe-Cys-Phe-(D)Trp-Lys-Thr-Cys-Thr-(ol)], were measured in two characterised transplantable tumours: a) the Swarm rat chondrosarcoma, known to be insulin-, growth hormone (GH)-, somatomedin- and corticosteroid-dependent, b) a hamster insulinoma, bearing specific high affinity somatostatin receptors. SMS 201-995 (1.25 mg/kg/day) given for 25 days to rats bearing freshly transplanted chondrosarcomas inhibited tumour volume by 48%. A significant tumour growth inhibition was measured also in well developed tumours treated with high doses of SMS 201-995 (1.25mg/kg/day) for 7 days. In the treated animals, GH was significantly inhibited. In hamsters bearing a freshly transplanted insulinoma, the daily application of SMS 201-995 (200 micrograms/kg/day, sc) for 33 days could significantly inhibit the growth (as measured by tumour volume) of the tumour. A moderate inhibitory effect of SMS 201-995 on the growth of well grown insulinomas could also be observed. This study shows that SMS 201-995 under the present experimental conditions has a moderate but significant growth inhibitory effect in two different transplantable tumour models. In the rat chondrosarcoma, the effect of SMS 201-995 is probably indirect, due to inhibition of GH, somatomedin and insulin. In the hamster insulinoma, the effect is possibly due to a more direct action of SMS 201-995 on specific somatostatin receptors present in this tumour.

The history of anabolic steroids and a review of clinical experience with anabolic steroids.

Abstract: Metabolism is the term employed to embrace the various physical and chemical processes occurring within the tissues upon which the growth and heat production of the body depend and from which the energy for muscular activity, for the maintenance of vital activity and for the maintenance of vital functions is derived (Best & Taylor 1950). The destructive processes by which complex substances are converted by living cells into more simple compounds are called catabolism. Anabolism denotes the constructive processes by which simple substances are converted by living cells into more complex compounds, especially into living matter. Catabolism and anabolism are part of all metabolic processes, the carbohydrate, fat and protein metabolism. The term anabolic refers only to substances that exert an anabolic effect on protein metabolism and are unlikely to cause adverse androgenic effects. They shift the equilibrium between protein synthesis and degradation in the body as a whole in the direction of synthesis, either by promoting protein synthesis or reducing its breakdown. The protein anabolic effect of anabolic steroids is not restricted to single organs but is the result of stimulated biosynthesis of cellular protein in the whole organism.

Median charge and charge heterogeneity of human pituitary FSH, LH and TSH

Abstract: The charge and charge heterogeneity of FSH, LH and TSH in 63 extracts of individual human pituitaries were investigated by use of zone electrophoresis in 0.17% agarose suspension in veronal buffer at pH 8.6 followed by hormone analyses by radioimmunoassay. The migration velocities are similar to those in free solution and directly proportional to differences in charge in the buffer. The technique gave highly reproducible results and the recovery of hormone activity after electrophoresis was about 100%. Methods for estimation of median charge, expressed as median migration rate, and of degree of charge heterogeneity are described. Each pituitary contained a sequence of different forms, estimated at 20 or more, of each of the three hormones, with minor differences in charge. The degree of charge heterogeneity within the pituitary was similar for FSH, LH and TSH. The distribution curves of radioimmunological activity in relation to migration rate were close to normality for the three glycoprotein hormones. This was in contrast to that found for Prl and GH. The merits of the electrophoretic technique are discussed.

Median charge and charge heterogeneity of human pituitary FSH, LH and TSH. II. Relationship to sex and age.

Abstract: The median charge and the degree of charge heterogeneity of FSH, LH and TSH in extracts from pituitaries of 63 individuals were determined by electrophoresis in 0.17% agarose suspension at pH 8.6 followed by hormone analyses by radioimmunoassay. Charge was expressed as migration rate in relation to that of human serum albumin. FSH, LH and TSH showed similar degrees of charge heterogeneity within the pituitary, and this degree of heterogeneity was not related to sex or age. There was a sex- and age-related variation in median charge of FSH and LH but not of TSH. The forms of FSH and LH were more acidic at higher ages and the most acidic forms were found in elderly women. Women 32 to 47 years old had more acidic forms of FSH than those 14 to 20 years of age. The median charge of LH was similar in young men and women, while that of FSH was more basic in young women than in young men. These results indicate that the effect of gonadal feedback on the molecular charge is different for FSH and LH. Studies with neuraminidase-treated pituitary extracts indicated that the sex- and age-dependent variations of the charge on FSH were due to differences in the sialic acid content. The amount of FSH in the pituitary was significantly smaller in men than in women. The contents of TSH and LH in the pituitary were lower in the higher age groups. No such decrease with age was found for FSH.

Circannual concentrations of melatonin, gonadotrophins, prolactin and gonadal steroids in males in a geographical area with a large annual variation in daylight.

Abstract: This study was aimed at elucidating the possible effects of a large annual variation in photoperiodicity on the secretory activities of the pineal gland, pituitary and testes. Serum daytime melatonin, FSH, LH, prolactin (Prl), testosterone and oestradiol concentrations were determined monthly over a year in 24 healthy young adult men (except for melatonin which was analysed only in 11 subjects) in northern Finland, where the day length is 22 h in mid-summer and 3.5 h in mid-winter. Serum daytime melatonin levels showed two annual peak values, in December and May, and a nadir was observed in August. The absolute values of the other hormones measured did not show significant month to month variation over the observation period. When hormone levels were calculated as percentages of the individual annual means, several significant differences were found between monthly levels. The melatonin peak in May (133 +/- 20%, SE, of the annual mean) was associated with significant increases in LH (110 +/- 4%) and FSH (107 +/- 3%). Prl levels (115 +/- 9%) reached a maximum in January. The nadirs of melatonin and the pituitary hormones measured were seen in August. Oestradiol showed the highest values in April-June, but no significant variation was found in serum testosterone levels. Positive correlations were observed between FSH and LH (r = 0.41, P less than 0.01), and Prl and LH (r = 0.26, P less than 0.01), whereas Prl and testosterone (r = -0.17, P less than 0.01) were inversely correlated.(ABSTRACT TRUNCATED AT 250 WORDS)

Physiological dosing of exogenous ACTH.

Abstract: We evaluated the ACTH and cortisol responses to several doses of exogenous ACTH, and compared these values to the physiologic responses obtained in normal subjects undergoing insulin-induced hypoglycaemia. We determined that a cosyntrophin dose of 0.2 micrograms/kg body weight produced both ACTH and cortisol levels indistinguishable from the 'physiologic' stress-induced values. Since this dose is approximately 4 per cent of the standard 250 micrograms dose employed in tests of adrenal function, our findings suggest a need for caution in the interpretation of such tests.

Gonadotrophins and ovarian steroids in cattle. I. Pulsatile changes of concentrations in the jugular vein throughout the oestrous cycle.

Abstract: Short-term secretion patterns of LH, FSH, progesterone and oestradiol-17 beta were evaluated throughout complete oestrous cycles of 6 heifers. Frequent blood samples (in 20-min intervals for 12 continuous h) were taken every 3-5 days from indwelling jugular catheters. There was a high incidence of concomitant LH and FSH pulses ranging from 72% at luteolysis to 83-100% during the luteal phase. Almost the same total number of LH and FSH pulses occurred during the early luteal phase (7.0 vs 7.4/12 h, respectively), however, there was an average of one additional FSH pulse in between the synchronous LH/FSH ones during the mid- and late luteal phase (6.9 FSH vs 3.4 LH pulses/12 h). Basal LH and FSH concentrations remained unchanged from the early until the late luteal period. During and after luteolysis frequency of LH and FSH release (14.5 vs 10.5 pulses/12 h) increased considerably as well as basal concentrations and magnitude of LH pulses. Secretion of both gonadotrophins persisted very frequently (13.3 LH and 10.7 FSH pulses/12 h) during pro-oestrus and oestrus when basal FSH concentrations and FSH pulse maxima approached a nadir. During the mid-luteal phase 45% of pulsatile progesterone occurred concomitantly with each coinciding LH/FSH pulse and 44% of pulsatile progesterone happened after additional single FSH pulses. Distinct short-term changes of oestradiol concentrations were not observed in the jugular vein but concentrations fluctuated randomly ranging from 2-6 pg/ml throughout the luteal period. Prior to and during heat mean concentrations of oestradiol were approximately 2-fold higher (P less than 0.05) than during the other periods of the cycle. It is concluded that the frequency of pulsatile LH release is modulated to a much greater extent than FSH by negative feedback of ovarian steroids. Some pulsatile progesterone secretion resulting from the stimulation of FSH (and LH) is still detectable in the jugular vein whereas of oestradiol-17 beta is not. The additional frequent monitoring of FSH might be more appropriate reflecting pituitary and hypothalamic function than only measuring LH.

Age- and sex-associated modification of plasma melatonin concentrations in man. Relationship to pathology, malignant or not, and autopsy findings.

Abstract: Plasma melatonin concentrations were determined in 757 unselected elderly patients aged 80.9 +/- 9.7 years. The daytime (8-9.30 h) plasma levels of melatonin were in the so-called normal range in only one third of the population whereas 65% of the subjects had abnormal levels of the hormone, most often decreased i.e. less than 0.17 nmol/l (53%) and sometimes increased i.e. 0.43 nmol/l or higher (12%). A control group of healthy elderly subjects showed the same distribution as the entire population. A sex-difference with significantly higher levels of plasma melatonin in elderly women was observed. With respect to pathology and autopsy findings high levels of the hormone correlated with cancer, chronic renal failure, cardiovascular disease, biological inflammatory syndrome and diabetes. Low levels correlated with neurologic disease, tobacco or alcohol addiction. However, some of these relations were found to be sex-related as they were observed in women but not in men. Our data indicate that pineal function seems to be often altered in elderly human subjects and suggest potential diagnostic applications of melatonin determination.

Serotonergic regulation of prolactin and growth hormone secretion in man.

Abstract: Controversy still exists regarding the role of serotonin in the regulation of prolactin (Prl) and growth hormone (GH) secretion in man. We gave healthy male volunteers three oral doses (0.5, 1.0 and 1.5 mg/kg) of fenfluramine, a serotonin-releasing agent and uptake inhibitor, and a corresponding placebo. There was a significant dose-response effect of fenfluramine on Prl but not on GH levels. Following the highest dose of fenfluramine, mean Prl levels increased from 9.7 ng/ml to 42.3 ng/ml. In a separate study, subjects were pre-treated with cyproheptadine, a serotonin antagonist, before the administration of fenfluramine. Cyproheptadine did not significantly affect basal Prl or GH levels, but it did blunt the response of Prl to fenfluramine. Cyproheptadine pre-treatment did not alter plasma levels of fenfluramine. Our findings support a stimulatory role for serotonin in the regulation of Prl secretion in man. They also suggest that serotonin does not have a major influence on GH secretion in man.

Treatment of myxoedema coma--factors associated with fatal outcome.

Abstract: Treatment of myxoedema coma has been associated with a high mortality. The causes of death were analysed in this paper by retrospective study of the records of 11 myxoedema coma patients. The serum thyroxine (T4) and triiodothyronine (T3) levels were estimated retrospectively from the amounts of hormone given to the patients by a two-compartment model. Seven patients died and 4 survived. The patients who died were significantly older (78.9 +/- 2.2 years, mean +/- SEM) than those who survived (66.8 +/- 3.7 years). The initial heart rate was lower in the decreased group, but both groups had increased their heart rate on treatment. The surviving patients showed an increase in body temperature during the first 3 days of treatment, in contrast to the patients who eventually died. The deceased patients had received larger amounts of thyroid hormone and had calculated levels of T3 that were nearly twice as high as those of the surviving patients. Old age and a high serum level of T3 are determinants for the fatal outcome of myxoedema coma. Our analysis underscores the importance of using a cautious replacement regimen in myxoedema coma patients.

Oxytocin determination in steroid producing tissues and in vitro production in ovarian follicles.

Abstract: Immunoreactive oxytocin was measured in ovaries (corpus luteum and follicular fluid) and adrenals of cows, and in testes, seminal vesicles, prostate gland and adrenals of bulls. Secretion of oxytocin was further measured after culture of whole follicles, granulosa cells and theca tissue. Concentrations of oxytocin increased in corpora lutea of cycling cattle until mid-luteal phase (447 +/- 93 ng/g wet weight) and decreased afterwards. Low concentrations were found in corpora lutea of pregnant animals (6 +/- 3 ng/g wet weight). Follicular fluid contains some oxytocin (on average 42-108 pg/ml) but concentrations were significantly higher in the fluid of ovarian cysts (190 pg/ml). After culture of follicles the amount of oxytocin released into the medium increased indicating de novo synthesis. The granulosa cells were the main source of follicular oxytocin. Production increased during luteinization indicating that luteinization is an important step for the production of oxytocin in ovaries. Tissues of testes (65 +/- 10 pg/g wet weight) and adrenals from cows (122 +/- 39 pg/g wet weight) and bulls (111 +/- 2 pg/g wet weight) contained oxytocin but at much lower concentrations compared to corpus luteum tissue. About 10 times higher concentrations of oxytocin were measured in the adrenal medulla (717 +/- 96 pg/g wet weight) compared to the cortex (72 +/- 11 pg/g wet weight). Seminal vesicles and prostate gland contained no measurable amounts of oxytocin (less than 5 pg/g wet weight).

Endocrine effects of high-dose ketoconazole therapy in advanced prostatic cancer.

Abstract: The endocrine effects of ketoconazole (400 mg orally every 8 h) were studied in 9 previously untreated patients with advanced prostatic cancer. Five of these patients were followed for 12 months. A rapid fall in the serum concentration of testosterone was noted in all patients studied. Minimal values were observed on day 4 of treatment but thereafter serum testosterone increased slowly. The effect of the drug on unbound testosterone was relatively more important, since sex hormone binding globulin increased markedly during treatment. An increase in progesterone and LH was observed in all patients. This suggests that ketoconazole limits the conversion of C21-precursors into androgens. This block is compensated in part by activation of the hypothalamo-hypophyseal feedback system. Urinary 17-ketosteroids were decreased but 17-hydroxysteroids were unaffected by the treatment. In 5 patients followed monthly over a period of 12 months the mean testosterone concentration ranged from 69 ng/100 ml in one patient to 428 ng/100 ml in another. An excellent inverse correlation could be demonstrated between the mean serum concentration of testosterone and the mean concentration of ketoconazole. The change of serum dehydroepiandrosterone sulphate also correlated inversely with the mean ketoconazole level. Increased concentrations of oestradiol were noted in 2 patients with slight gynaecomastia. It is concluded that long-term suppression of androgen production can be realized by high-dose ketoconazole treatment and that the degree of suppression is proportional to the serum levels of the drug.

Catch-up growth following transfer from three times weekly im to daily sc administration of hGH in GH deficient patients, monitored by knemometry

Abstract: A novel and non-invasive technique of growth measurement is introduced. By this method the length of the human lower leg is measured with an accuracy of 0.1 mm. Thus, growth velocities can be estimated within a few weeks. In the present study the immediate changes of growth velocity are demonstrated, following the transfer of growth hormone administration from three times weekly im to daily sc in 9 growth hormone deficient children, age 7.4 to 20.5 years. The first observation period (3 times weekly im administration) ranged from 32 to 72 days, the second observation period (daily sc administration) ranged from 160 to 267 days). During the study, the total weekly dosage of growth hormone remained unchanged (12 IU/m2/week). In all 9 patients growth velocity increased significantly after the transfer of application. Mean growth velocity of the lower leg rose from 0.04 mm/day up to 0.065 mm/day. Mean growth velocity of total body height rose form 4.8 cm/year up to 6.9 cm/year. In addition, differential lower leg growth rates of 3 to 4 week periods were established in all 9 patients, revealing a significant catch-up growth spurt immediately following the transfer of application. During this spurt mean lower leg growth velocity rose form 0.04 mm/day up to 0.091 mm/day. This marked increase of lower leg growth rates lasted for only a few weeks and was followed by a period of decreased growth velocity. On the long run, growth velocity shifted upward in a wave-like pattern, stabilizing on a significantly higher level than before the transfer of application.

Contribution of individual compartments of the genital tract to oestrogen and testosterone concentrations in ejaculates of the boar

Abstract: The investigation of steroids in compartments of the genital tract of boars revealed that in the tubular fluid a pattern apparently exists which is unique in this compartment. It is characterized by high concentrations of unconjugated testosterone (35 ng/ml) and even higher amounts of oestradiol-17 beta (42.6 ng/ml) whereas in other compartments oestrone is the predominant oestrogen. At least in the ejaculate half of the total amount of oestrogens is bound to sperms and it is concluded that sperms act as a carrier for oestrogens. The accessory sex glands contribute to ejaculate concentrations to a varying degree (unconjugated testosterone 55%, conjugated testosterone 20%, unconjugated oestrogens 22%, conjugated oestrogens 12%) as could mainly be demonstrated by vasectomy with and without administration of hCG. Increasing the frequencies of ejaculations (up to three times a day) shows that the steroid transfer into the ejaculate is a rapid process.

Effect of insulin on porcine granulosa cells: implications of a possible receptor mediated action.

Abstract: The mechanism of direct action of insulin on porcine granulosa cells cultured in vitro was investigated. Specific receptors for insulin with two classes of binding sites were present. No significant difference in receptor characteristics was observed between granulosa cells obtained from small (1-2 mm), medium (3-5 mm) or large (6-11 mm) follicles. Insulin (25 mIU/ml) augmented both basal and hCG-stimulated progesterone secretion. Insulin was also essential for hCG-stimulated morphological luteinization of cultured porcine granulosa cells obtained from small follicles. Furthermore, 2 h pre-incubation with insulin (100 mIU/ml) increased glucose incorporation by cultured porcine granulosa cells as determined by pulsing with D-[14C](U)-glucose. The same dose of insulin also stimulated the glucose-6-phosphate independent form of glycogen synthase. These results suggest that porcine granulosa cells possess insulin receptors and that insulin, mediated by its specific receptors, enhances glucose metabolism by stimulating glycogen synthase. Thus, insulin may play a pivotal role in morphological and functional differentiation of porcine granulosa cells.

Mortality and associated risk factors in diabetics.

Abstract: In 168 male diabetics aged 40-64 years participating in the Whitehall Study, ten-year age adjusted mortality rates were significantly higher than in non-diabetics for all causes, coronary heart disease, all cardiovascular disease and, in addition, causes other than cardiovascular. Mortality rates were not significantly related to known duration of the diabetes. The predictive effects of several major mortality risk factors were similar in diabetics and non-diabetics. Excess mortality rates in the diabetics could not be attributed to differences in levels of blood pressure or any other of the major risk factors measured.

Nocturnal high-dose dexamethasone suppression test in the aetiological diagnosis of Cushing's syndrome

Abstract: Seventeen patients with well-proven Cushing's syndrome (13 with Cushing's disease, 3 with adrenal tumour and 1 presenting ectopic ACTH syndrome caused by bronchial carcinoid) were investigated by using a single-dose 8 mg dexamethasone nocturnal test. The results obtained were compared with those of the classical 8 mg Liddle's test, metyrapone stimulation, plasma ACTH concentration and with the final diagnosis reached through surgery, pathologic anatomy, and/or clinical and biochemical follow-up of the patients after treatment. The diagnostic efficacy or the predictive power of the test (defined as the ratio between the number of cases in which the diagnosis was correctly predicted and the total number of cases), was at least 82.4% vs 84.6% for the classical 8 mg Liddle's test. This percentage increased to 94.1% when the results of repeated tests on three patients with conflicting data were included. It is concluded that the nocturnal high-dose dexamethasone suppression test is a valuable tool in the aetiological diagnosis of Cushing's syndrome.

The mechanism of hypocalcaemia following thyroidectomy

Abstract: The mechanism of transient hypocalcaemia following thyroidectomy was studied in 29 consecutive patients undergoing thyroid surgery. Eight of 27 (30%) patients who had a partial thyroidectomy developed transient hypocalcaemia. Hypocalcaemia was attributable to a reduction in renal tubular reabsorption of calcium (P less than 0.05), but was not associated with changes in serum values of immunoassayable parathyroid hormone or calcitonin.

Aminoglutethimide and metyrapone in the management of Cushing's syndrome.

Abstract: Fifteen patients with endogenous Cushing's syndrome were treated with metyrapone and/or amino-glutethimide. The duration of the therapy varied from 19 up to 365 days. In patients with Cushing's disease, metyrapone (0.5-2.5 g/day) and aminoglutethimide (0.5-1.5 g/day) seemed equally effective in reducing the cortisol excretion (54 +/- 9 vs 40 +/- 7%). The majority of these patients also showed a clinical improvement. In 1 patient with adrenal adenoma, metyrapone induced a remission. In another patient with adrenocortical cancer, and in 2 with the ectopic ACTH syndrome, the cortisol excretion was significantly reduced by the combination of metyrapone and aminoglutethimide but no obvious clinical improvement was observed. Side effects i.e. rash and pruritus attributed to aminoglutethimide was seen in 3 patients which necessitated the omission of treatment in 2. On metyrapone a moderate hypertrichosis was observed in 1 patient. In conclusion both metyrapone and aminoglutethimide were useful as adjunctive therapy in Cushing's syndrome.

In vitro degradation of angiotensin II (A-II) by human placental subcellular fractions, pregnancy sera and purified placental aminopeptidases

Abstract: The degradation of angiotensin II (Asp1-Arg2-Val3-Tyr4-Ile5-His6-Pro7-Phe8: A-II) by human placental particulate and soluble fractions, pregnant and non-pregnant sera, and highly purified placental enzymes such as placental leucine aminopeptidase P-LAP (microsomal), retroplacental serum P-LAP (soluble), aminopeptidase A and post-proline endopeptidase, was studied by measuring liberated amino acids by high performance liquid chromatography Placental particulate and soluble fractions degraded A-II almost completely into single amino acids The purified P-LAP (microsomal) actively liberated five amino acids from the N-terminal The placental particulate fraction containing P-LAP (microsomal) also actively liberated these amino acids The purified aminopeptidase A liberated Asp1 very actively as expected When the ratio of the velocity of liberation of each amino acid to P-LAP activity measured with leu-p-nitroanilide as a substrate was calculated, placental soluble fraction liberated Asp1 very actively, but the liberation rate of Asp1 with the purified P-LAP (soluble) was very low Therefore it seems that the enzyme in the placental soluble fraction and pregnancy serum responsible for the Asp1 liberation is not P-LAP (soluble), but aminopeptidase A The mixture of purified P-LAP (soluble) and aminopeptidase A showed higher liberation rate of Arg2 and Val3 than that with purified aminopeptidase A alone, demonstrating that once the N-terminal Asp1 was liberated, the P-LAP (soluble) attacks the shorter peptide (angiotension III) very actively It was concluded that P-LAP (microsomal) together with aminopeptidase A seem to contribute greatly to the degradation of A-II in pregnant women

Changes in circadian rhythm and suppression of the plasma cortisol level after prolonged stress in the sheep.

Abstract: Diurnal variations in the plasma cortisol level were studied in anoestrous, pro-oestrous and pregnant ewes subjected to weak electric stimulation of the fore-limbs 9 h daily for 3 consecutive days. In non-pregnant ewes the cortisol level rose on each of the 3 days when the stimulation was applied and then decreased on the day following the stimulation. A similar decrease in plasma cortisol concentrations in pregnant ewes appeared on the second day of footshocking. The acrophase of the circadian rhythm on electrostimulation days was synchronous with the time of application of footshocks; therefore, in stimulated ewes it was significantly accelerated compared to the prestimulatory day. A decrease in the plasma cortisol level in pro-oestrous and pregnant ewes was accompanied by disappearance of its normal rhythmicity. Since a normal plasma cortisol response to exogenous corticotrophin was noted after 3 days of footshocking it seems unlikely that the decrease in the cortisol level after prolonged stress was caused by exhaustion of the adrenal cortex. Some central mechanisms which could account for the biphasic changes in the plasma cortisol level and for disturbances of the hormone diurnal rhythmicity under conditions of prolonged stress are discussed.

Plasma concentrations of 1-deamino-8-D-arginine vasopressin after intragastric administration in the rat

Abstract: A sensitive and specific radioimmunoassay for 1-deamino-8-D-arginine vasopressin (DDAVP) was developed. Plasma concentrations of DDAVP after intragastric administration were determined in non-fasted rats and a dose-related increase in plasma levels was obtained. The immunoidentity of plasma DDAVP and standard was established by high performance liquid chromatography (HPLC). Correlation of biological and immunological responses of DDAVP was assessed using the antidiuretic effect in the Brattleboro (diabetes insipidus) rat.

Effects of insulin-like growth factors on chick embryo hepatocytes.

Abstract: Biological effects of insulin-like growth factors (IGF) I and II on primary cultures of chick embryo liver cells have been investigated and compared 1) with the biological effect of insulin and 2) with competitive binding of the three hormones to their respective binding sites IGF I and II stimulate the incorporation of D[U-14C]-glucose into liver cell glycogen in a time- and dose-dependent manner, but with a 5-10-fold lower potency than insulin Both IGFs also lead to enhanced incorporation of 5-[3H]uridine and L[U-14C]valine into trichloroacetic acid (TCA) insoluble material and to activation of ornithine decarboxylase activity Their potency in stimulating RNA synthesis and ornithine decarboxylase activity is comparable to that of insulin Protein synthesis is maximally stimulated at 3 nM by all three hormones In the competitive binding studies, IGF I and II are 10-fold less potent than insulin in competing for [125I]insulin binding, but 100-fold more potent than insulin in competing for [125I]IGF I or II binding These studies show that IGF I and II stimulate the same metabolic indices as insulin in the chick embryo liver By comparing these biological effects with competitive binding data it appears that IGFs act on glucose metabolism in the chick embryo liver via the insulin receptor, whereas stimulation of growth indices by IGFs and insulin appears to be mediated by their own specific receptors

Progression of cardiovascular disease in acromegalic patients treated by external pituitary irradiation.

Abstract: Cardiovascular complications are a major cause of morbidity and mortality in acromegaly and seem to be related to the long duration of the disorder. Conventional external pituitary irradiation for acromegaly produces a consistent, but slow, fall in elevated serum growth hormone (GH) levels. It has not been established whether such treatment is effective in preventing the development of cardiovascular complications. The evolution of cardiovascular disease has therefore been studied in 11 acromegalic patients followed up for a mean 10 years (range 3-17) after external pituitary irradiation. At the final follow-up fasting serum GH were significantly (P less than 0.01) lower than pre-irradiation levels, but cardiovascular events (myocardial infarction, dysrhythmias, hypertension, major arterial disease, heart failure) increased significantly in prevalence (P less than 0.01) during this period. Electrocardiographic abnormalities also increased in prevalence. At the final follow-up 6 patients had cardiomegaly on chest X-ray and echocardiographs (10 patients) were abnormal in every case. All 11 patients had evidence of complete or partial anterior hypopituitarism. We confirm that external pituitary irradiation is effective in reducing elevated serum GH levels in acromegaly, but suggest that such a slow reduction in serum GH levels does not retard the development of cardiovascular complications.

Comparison of histology and immunohistochemistry with thyroglobulin serum levels and radioiodine uptake in recurrences and metastases of differentiated thyroid carcinomas.

Abstract: The importance of lightmicroscopical and immunohistochemical features of 38 recurrent differentiated thyroid carcinomas (27 papillary carcinomas (PC), 11 follicular carcinomas (FC] for post-operative serum thyroglobulin (TG) concentrations was analysed in regard to pre-operative serum TG levels with tumour type, histological and cytological differentiation, volume fraction of TG synthesizing tumour cells (TG immunohistomorphometry), tumour volume and radioiodine uptake (RIU). Serum TG concentrations increased with tumour size and the number of TG synthesizing tumour cells (r = 0.5). PC and FC did not differ in their volume proportions of TG synthesizing tumour cells, while TG serum levels in FC significantly exceeded those of PC of similar size. The low TG serum levels found in PC might be explained by a specific defect in thyroglobulin secretion. Carcinomas with partial or total cytologic metaplasia (e.g. oxyphilic carcinomas) had low volume proportions of TG synthesizing cells and low serum TG levels. Thirteen of the 38 differentiated carcinomas (34.2%) showed both high TG serum levels and positive RIU, 17 (44.7%) disclosed only elevated TG serum levels and 6 (15.8%) a positive RIU. In two cases (5.3%) TG serum levels were not elevated and RIU's were negative. TG immunostaining was positive in all 38 cases. In summary, TG serum levels depend on the following morphologic factors in differentiated thyroid carcinomas: 1) Number of TG synthesizing tumour cells, 2) Mode of TG secretion and 3) Cytological differentiation of the tumour cells. Serum TG levels did not predict total body iodine scan.