bluuebunny/crossref_metadata_2025 huggingface dataset:
EFFECT OF THYROTROPHIN RELEASING HORMONE AND THYROID-STIMULATING HORMONE ON SERUM PROTEIN-BOUND 131I
Authors: Haug Egil , Frey Harald , Sand Terje
Published: December 2008

Seventeen subjects without any clinical or laboratory evidence of thyroidal or pituitary disease were given 1.0 mg thyrotrophin-releasing hormone (TRH) as a rapid iv injection 48 hours after an oral dose of 50 μCi 131I-. In all subjects there was a clear rise in serum PB131I. The elevation in the mean serum PB131I was significant (P<0.01) one hour after TRH, and the mean peak response was noted at 4 hours. It is suggested that this elevation in serum PB131I following TRH administration reflects the effect of the TSH released. In order to find the most suitable method of administration, 1.0 mg TRH was given iv, im, or as a 1 hour infusion. The maximal responses seemed to be independent of the mode of administration. Six subjects were given 3.0 mg TRH iv and 4 others 6.0 mg TRH iv. It was not possible to demonstrate a clear dose-response relationship. In five subjects the serum PB127I and the serum PB131I were measured at the same times following administration of TRH. This showed that the serum PB131I was a more sensitive index of TSH release than the serum PB127I. Twenty-four hours after the TRH injection the same subjects were given 5 IU TSH as a rapid iv or im injection. All subjects responded with a significant rise in serum PB131I. In the subjects who did not respond to TRH the response to TSH allows the differentiation between pituitary and thyroid disease.
ALDOSTERONE ACTION ON THE PAROTID GLAND: SODIUM REPLETE SHEEP
Authors: Kraintz L. , Blair-West J. R. , Coghlan J. P. , Denton D. A. , Wright R. D.
Published: December 2008

Aldosterone was infused intravenously at 30 μg/h into sodium replete adrenalectomised sheep which caused salivary [K] to rise to 14–45 mEq./l. After 4 h the animals were anaesthetised and the parotid duct cannulated. With salivary [K] at 14–45 mEq./l, stimulation of the sympathetic nerve supply to the gland caused rapid expulsion of ½-1 ml of saliva with a [K] of 4–8 mEq./l, the normal for sodium replete level. It is concluded that in the sodium replete animal, aldosterone acts on Na+ – K+ exchange sites in the ducts only.
EFFECT OF THYROCALCITONIN ON ALKALINE PHOSPHATASE AND PYROPHOSPHATASE IN RAT TIBIA, KIDNEY AND INTESTINE
Authors: Streifler Cipora , Orenstein Arie , Harell Arieh
Published: December 2008

The influence of thyrocalcitonin (TCT) on the enzymes alkaline phosphatase and inorganic pyrophosphatase in rat bone, kidney and intestine was studied.

The rats were injected with TCT every hour for 4 hours. They were divided into groups and were sacrificed 1 h after the first, second, third and fourth injection respectively. The plasma calcium was found to be reduced. Enzyme studies showed that: a) in tibia metaphysis homogenates alkaline phosphatase increased in response to TCT, to 198, 175, 154 and 183 per cent of the non-injected rats after 1, 2, 3, and 4 injections, respectively; inorganic pyrophosphatase was elevated to 356, 209, 221, 425 per cent after the same TCT injections. b) In kidney homogenates alkaline phosphatase was reduced to 75, 53, 79, 68 per cent of the non-injected rats after 1, 2, 3 and four doses, respectively; inorganic pyrophosphatase was reduced to 78, 56, 77 and 71 per cent after the same injections of TCT. c) In the jejunum, alkaline phosphatase was found to be 88.5, 71, 91 and 115 per cent of the untreated rats after 1, 2, 3 and 4 injections, respectively; pyrophosphatase in this tissue was found to be 105, 102, 102 and 113 per cent of the normal under the above conditions.

The results indicate: 1. TCT causes increases in alkaline phosphatase and inorganic pyrophosphatase activities in bone. The increase of pyrophosphatase is significantly more marked than the increase of alkaline phosphatase; 2. in kidney tissue, the action of TCT on these two enzymes is slower and their activities are equally reduced; 3. in the jejunum no significant effect of TCT on the activity of these two enzymes was observed.
IODINATED THYROLIPIDS
Authors: Shah D. H. , Shownkeen R. C. , Thakare U. R.
Published: December 2008

Sheep, bovine, mouse, dog and human thyroids incorporate 35–55% (41.5%, 45.9%, 34.4%, 55.4% and 41.1%, respectively) of total lipid radiodine in an unidentified polar thyrolipid fraction moving between phosphatidyl ethanolamine and phosphatidic acid on silica gel G thin layer chromatography in a solvent system CHCl3:MeOH:H2O (80:25:3). This unidentified lipid fraction (Fr. II) is ninhydrin negative, phosphorus negative, alkali labile, acid stable, phospholiphase A stable and orcinol positive indicating the absence of a free amino group, phosphorus group, vinyl ether linkage, vicinal phosphorus ester linkage and the presence of a sugar moiety.

Iodination of fraction II seems to be specific for the thyroid gland only, as the other iodide concentrating tissues such as the submaxillary salivary gland and stomach localise most of the radioiodine with phosphatidyl choline and lyso-phosphatidyl ethanolamine fraction respectively. Biologically inactive thyroid tissue or non-enzymic iodination of isolated thyrolipids indicate phosphatidyl choline and/or phosphatidyl ethanolamine as major iodinated lipid fractions. The possible role of fraction II in iodination for homornogenesis in thyroid tissue is discussed.
CONTRIBUTION TO THE EXISTENCE OF REGULATORY MECHANISMS AT THE ADRENAL LEVEL
Authors: Linèt Otto
Published: December 2008

Rat adrenal glands atrophied by the administration of cortisol acetate in vivo were used as a model for the study of early metabolic processes occurring in vitro. Atrophied adrenals incubated in the presence of 14C-leucine incorporated subnormal quantities of this amino acid per mg of protein for the first 120 min. When the incubation lasted for a total period of 180 or 240 min a supranormal rise in the 14C-leucine incorporation was observed. Similar changes occurred with some delay with regard to corticosterone production as expressed per 100 mg of tissue. No differences in 14C-leucine incorporation were observed between the control and atrophied adrenals in vivo. Homogenates from atrophied glands incorporated 14C-leucine to a greater extent than the control homogenates. The in vitro incorporation of 14C-orotic acid into the RNA was also higher in atrophied adrenals. The in vitro use of actinomycin D, cycloheximide and amphenone indicated that corticosterone production depended on the incorporation of 14C-leucine. The addition of cortisol to the incubation media markedly decreased the enhancement of 14C-lysine incorporation into the protein of atrophied adrenals. These, as well as additional results suggest rebound phenomena: once atrophic adrenals are transferred to cortisol-free media, reparative processes begin after a delay period. Such phenomena seem to be mediated by regulatory mechanisms at the adrenal level.
URINARY FOLLICLE STIMULATING HORMONE AND LUTEINIZING HORMONE IN NORMAL ADULT MEN
Authors: Christiansen Peter
Published: December 2008

The normal range of the excretion of follicle stimulating hormone (FSH) and luteinizing hormone (LH), as well as the relation between these values and those in aging subjects was investigated by specific bioassays in 50 normal adult men with an age range of 21 to 82 years. The FSH rose significantly but did not reach the levels observed in postmenopausal women. The LH showed no significant rise and consequently the FSH/LH ratio rose. Normal values and the 95% fiducial limits in the decades from 21 to 70 years are shown.
EFFECTS OF OESTROGEN ON THYROCALCITONIN ACTIVITY IN MALE AND FEMALE RABBITS
Authors: Currie G. N. , Black D. L.
Published: December 2008

Thyrocalcitonin is an effective hypocalcaemic agent in both the male and female Dutch Belted rabbit. In this strain of rabbit, a level of oestradiol (1 μg/kg of body weight) which is not hypercalcaemic and levels of oestradiol that are hypercalcaemic can effectively block the action of thyrocalcitonin in both the male and female.
COMPARATIVE STUDIES ON THE BINDING OF 131I-LABELLED AND UNLABELLED INSULIN TO RAT DIAPHRAGM IN VITRO
Authors: Bouman P. R. , Coert A. , Jaspers N. M. V.
Published: December 2008

Rat hemidiaphragms were incubated with either unlabelled or 131I and 127I-labelled insulin of varying degrees of iodination (0.08–1.4 I/mole). With all types of insulin the percentage disappearance of immunoreactive insulin (IRI) was found to exceed the percentage uptake of radioactive label by the tissue by a factor of 10. This discrepancy is attributed to degradation of labelled hormone taken up by the tissue, degradation of the hormone within the medium and reduced tissue-binding of iodinated insulin molecules.

Even after incubation for 15 min, fixation of labelled insulin to the diaphragm appeared to coincide with a return-flow of TCA-soluble labelled fragments into the medium. Washing of the diaphragm for 10 min resulted in a 30% loss of tissue-bound radioactivity. After incubation with unlabelled insulin less than 1% of the tissue-bound IRI could be recovered in the washing medium.

After correction for IRI degradation within the medium, the binding of iodo-insulin 1.4 I/mole to the diaphragm amounted to 56% of that of the unlabelled insulin. Since the biological activity at this degree of iodination appeared to be reduced by over 50% of the immunologic activity, it is suggested that the decreased activity of iodo-insulins may be due to the reduced affinity of the hormone to specific receptor sites involved in the initiation of the biological response.

The results of this study indicate that accumulation of the radioactive label of 131I-labelled insulin in incubated diaphragms gives no reliable quantitative index for the binding of either labelled or unlabelled insulin to this tissue.
ASPECTS OF CARBOHYDRATE METABOLISM IN NEWBORN INFANTS OF DIABETIC MOTHERS. III
Authors: Mølsted-Pedersen Lars , Jørgensen Kaj R.
Published: December 2008

Plasma insulin was determined during iv glucose tolerance tests performed 3 hours after birth in 54 newborn fasting infants comprising three groups: 26 infants of normal mothers, 11 infants of non-insulintreated diabetic mothers and 17 of insulin-treated diabetic mothers.

In the normal group a significant positive correlation was found between the fasting plasma insulin concentration and the birth weight. In all three groups a positive correlation was found between the birth weight and the insulin increase 12 min after the glucose injection (Δ I). Between Δ I and the disappearance rate of glucose (K value) a significant positive correlation was demonstrated in all three groups of infants.

Δ I was identical with the maximum increase in plasma insulin in the diabetic groups, while in the normal group a maximum did not occur until 50 min after the glucose injection.

Simultaneously obtained plasma samples from the umbilical vein, umbilical artery and heel stab demonstrated that reliable results of plasma insulin concentration could only be obtained from the umbilical vein.
EXPERIMENTAL STUDIES ON THE ENDOCRINE REGULATIONS DURING THE PERIOVULATORY PHASE OF THE HUMAN MENSTRUAL CYCLE
Authors: Leyendecker G. , Wardlaw Sharon , Nocke W.
Published: December 2008

In an attempt to simulate some parts of the progesterone and oestradiol patterns found in the normal menstrual cycle by intramuscular injections of microcrystalline progesterone and oestradiol benzoate, two distinct effects of progesterone and oestradiol on the hypothalamic cyclic centre were observed. Both progesterone and oestradiol can produce a positive feedback on the cyclic centre as measured by a plasma LH surge when administered to women with primary amenorrhoea, to castrated women, to women in the postmenopause and to eugonadal women receiving oral therapy of 60 μg of ethinyloestradiol per day. Subsequent LH peaks could be induced with progesterone or oestradiol benzoate after an oestradiol induced LH peak, but no further LH peak could be induced by either progesterone or oestradiol following a first progesterone induced LH peak. The progesterone induced LH discharge differed from that induced by oestradiol: It always occurred immediately after progesterone injection regardless of the dose given and was terminated very abruptly. The duration of the release of LH seems to decrease with an increase in the progesterone dose. In contrast, the first significant rise in the plasma LH concentration after oestradiol benzoate injection occurred after a latent phase of at least 24 hours. A significant FSH increase in the plasma was only seen following progesterone injection.

The results of these feedback studies are interpreted in conjunction with the steroid pattern of the human female menstrual cycle. 17β-oestradiol was suggested as the initial triggering stimulus in the cycle leading to an LH surge. This first LH surge may cause the pre-ovulatory luteinization of the theca interna, thus, resulting in an increase of plasma progesterone. The biphasic stimulatory and inhibitory feedback effect of progesterone provides the final dosage regulation of the total LH discharge by regulating the amount of LH released in the second part of the biphasic midcycle peak. Progesterone also blocks the cyclic centre to further stimulation during the luteal phase of the cycle. The biphasic feedback effect of progesterone is interpreted as a possible periovulatory mechanism for mono-ovulation in the human female.
URINARY EXCRETION OF DEHYDROEPIANDROSTERONE IN NORMAL AND ABNORMAL LATE PREGNANCY AND IN NON-PREGNANT WOMEN
Authors: Dässler C.-G.
Published: December 2008

The urinary excretion of dehydroepiandrosterone (DHA) in 10 healthy women during the last month of pregnancy (mean m = 0.43 mg/24 h; standard deviation sd = ±0.13) was found to be as high as that in 7 patients with chronic hypertension or with toxaemia of pregnancy (m = 0.40 mg/24 h; sd = ±0.13). The values were significantly (P < 0.01) decreased in 6 women in late pregnancy with intrauterine foetal death (m = 0.20 mg/24 h; sd = ±0.10), in two cases of pregnancy with anencephalic foetuses (0.30 and 0.25 mg/24 h, resp.) and in 11 healthy non-pregnant women (m = 0.26 mg/24 h, sd = ±0.10). The method used involved separation of free non-conjugated Zimmermann chromogens from the urine by extraction with benzene, mild hydrolysis of the urine, column chromatography on silica gel and colorimetric determination as Zimmermann chromogen. It is assumed that the increased excretion of DHA in the two groups of late pregnant women with intact pregnancy as compared with non-pregnant women may be caused by the biosynthesis of DHA in the foetal adrenals. The unchanged values of DHA in the two groups of women during late pregnancy with intrauterine foetal death or with anencephalics may reflect the interrupted biosynthesis of DHA.
THE EFFECTS OF A SYNTHETIC THYROTROPHIN RELEASING HORMONE (TRH) IN NORMAL AND ENDOCRINOPATHIC SUBJECTS
Authors: Faglia G. , Beck-Peccoz P. , Ambrosi B. , Ferrari C. , Travaglini P.
Published: December 2008

The effects of thyrotrophin releasing hormone (TRH) on plasma thyrotrophin (HTSH), thyroxine iodine (T4-I), growth hormone (HGH) and cortisol were studied in healthy and endocrinopathic subjects. In normal subjects rapid iv injection of 100, 200, 400, 600, 800 μg of TRH caused definite increases in plasma HTSH with a dose-response correlation between 100 and 200 μg; the peak occurred at 20–30 min at any dose level; iv infusion of 1000 μg over 30 min was followed by highly variable rises in plasma HTSH; the oral administration of 20 mg caused a definite and prolonged increase. In endocrinopathic subjects a standard dose of 600 μg of TRH was rapidly iv injected: 5 euthyroid patients with high 131I thyroidal uptake showed a normal increase in HTSH; 10 cases of Graves' disease, 5 of hyperactive adenomas as well as 4 normal subjects pre-treated with triiodothyronine showed no response; out of 5 cases of Graves' disease re-investigated after remission 3 showed no response, while 2 had an exaggerated response; 5 cases of primary myxoedema showed a very marked and prolonged response; out of 2 patients with idiopathic secondary hypothyroidism 1 did not respond at all and 1 showed a large and prolonged increase with a late peak; out of 4 cases of secondary hypothyroidism due to pituitary tumours, 2 gave normal responses, 1 showed a very marked and prolonged rise and 1 had a poor response; the same subject, after selective adenomectomy, however, had an exaggerated response; 12 euthyroid patients with pituitary tumours were examined: 3 did not respond at all, 4 had a normal increase in plasma HTSH and 5 gave a prolonged and exaggerated response. The serum T4-I showed an upward trend after TRH iv; however, the increase was not present in all instances. After oral administration of TRH a more definite increase was reached. It was demonstrated that TRH does not promote the release of HGH and ACTH.
DISTRIBUTION OF 14C-THIOURACIL IN THE THYROID AND THE ULTIMOBRANCHIAL GLAND OF CHICKENS STUDIED BY WHOLE-BODY AUTORADIOGRAPHY
Authors: Slanina Premysl
Published: December 2008

Whole-body autoradiography of chicks 10, 20, 240 minutes and 1 and 4 days atfer iv injection of 14C-thiouracil showed a rapid and high accumulation of radioactivity in the thyroid. The concentration of radioactivity in the thyroid was higher than in any other tissue and persisted for as long as 4 days after the injection. In contrast, the level of radioactivity in the calcitonin producing ultimobranchial gland never exceeded that of the blood, suggesting that thiouracil does not directly affect the release of calcitonin.
MEASUREMENTS OF 125I LABELLED METABOLITES IN HUMAN THYROID TISSUE
Authors: Agerbæk Hans
Published: December 2008

The results of paper-chromatographic separation and measurements of radioactive-labelled, iodinated metabolites in digested thyroid tissue depend to a great extent on the procedure chosen.

The purpose of the present study was to develop a valid and reproducible procedure for human thyroid specimens.

We have systematically evaluated the following steps in the procedure: 1) removal of representative tissue for mean distribution of 125I and [125I] aminoacids, 2) chromatography of undigested thyroid homogenate, 3) propylthiouracil (PTU) versus 1-methyl-2-mercaptoimidazole (MMI) in the digest buffer, 4) digestion time using Pronase, 5) digestion of »whole« versus centrifuged homogenate, 6) chromatography of »whole«-digest versus supernatant of centrifuged digest, 7) chromatography in acid and alkaline solvents.

Based on this investigation the following standard procedure was chosen: Representative tissue specimens were homogenized in Tris-acetic acid buffer 0.2 m, pH 8.6 containing PTU 7 × 10−4 m, tissue concentration 40 mg/ml. »Whole«-homogenate was digested at 37°C for 24 hours with added Pronase 4 mg/ml + toluol. »Whole«-digest was applied to Whatmann 3 MM paper for approximately 10 hours of ascending chromatography. The solvent used was n-butanol-ethanol-ammonia 0.4 n (15:3:6). The standard procedure was checked by 65 duplicate estimations and found to be highly reproducible. Extensive recovery experiments with in vitro added [125I] aminoacids and Na125I revealed a total radioactivity recovery of 96% for DIT, 93% for MIT, 95% for I−, 98% for T4 and 90% for T3. The relative recovery, an expression of the stability of individual compound, was about 100% for MIT, DIT and I−, but only 75% for T4 and 77% for T3.
IODIDE-INDUCED GOITRE AND HYPOTHYROIDISM IN A PATIENT WITH CHRONIC LYMPHOCYTIC THYROIDITIS
Authors: Liewendahl K. , Turula M.
Published: December 2008

Goitre due to the ingestion of excess iodide is a comparatively rare disorder. About two hundred cases of sporadic iodide goitre have been reported. In two of these cases an underlying chronic lymphocytic thyroiditis was verified histologically or cytologically. This paper describes another case of iodide goitre after prolonged intake of seaweed tablets in a female with histologically verified chronic lymphocytic thyroiditis. The discussion is concerned with the mechanism of development of iodide goitre and the possible interrelationship between thyroiditis and the intake of excess iodide in the patient studied.
DYNAMICS OF HEPATIC GLYCOGEN: OESTROGEN AND PREGNANCY
Authors: Paul P. K.
Published: December 2008

The effects of oestradiol (0.5 μ/rat/day) given for a variable period on rat liver were investigated, and the results were compared with those of untreated pregnant rats at different stages of pregnancy. The part played by the adrenal under these conditions was also investigated. Oestrogen treatment for 14 and 21 days in intact rats reduced the liver glycogen. A corresponding reduction in food intake was noted during these days. However, a rebound rise in liver glycogen occurred after 28 days of oestrogen administration. In contrast, the ovariectomized animals did not show any change in liver glycogen following steroid treatment. During pregnancy the total liver glycogen increased after the first week, but returned to the normal level on day twenty one. The adrenal and serum cholesterol levels in oestrogen treated and pregnant rats remained low except for an increase in serum cholesterol on day 21 of gestation and 7 days after oestrogen treatment. The study suggests that continued oestrogen treatment of non-pregnant rats probably maintains some endogenous factor(s) (progesterone) for about 21 days, which antagonizes the effect of oestrogen administration on hepatic glycogen deposition. The implications of liver glycogen changes during pregnancy in relation to progesterone levels and dietary intake are discussed.
FORMATION OF 5α-REDUCED PRODUCTS FROM TESTOSTERONE IN VITRO BY GERM CELLS FROM IMMATURE RATS
Authors: Yamada Morio , Yasue Shunji , Matsumoto Keishi
Published: December 2008

In the incubation study of [3H] testosterone with tissue homogenates in the presence of NADPH, it was shown that the rate of production of the sum of all 5α-reduced products by 30-day-old rat testes (50 to 100 nmoles/g tissue or 100 mg protein/h) was of the order of twenty times that by the ventral prostate (2 to 4 nmoles/g tissue/h). The activities of the C19-steroid Δ4-5α-reductase of the seminiferous tubules, germ cells and tubular non-germ cells isolated from immature rats (7 to 10, 11 to 13 and 5 to 7 nmoles/100 mg protein/h, respectively) were of similar order to those of the prostate, while much less activity was found in the spleen and muscle. It was also noted that the activity of the 5α-androstane-3α-, and -3β-hydroxysteroid dehydrogenase seemed to be higher in each tissue of immature rat testes than in the prostate tissue. The seminiferous tubules were isolated by collagenase treatment and germ cells were separated from non-germ cells by tubular cell culture at 34°C for 2 days. Thus, germ cells of immature rat testes seem to have the characteristics of androgen responsive tissue.
HORMONAL STUDIES IN A PATIENT WITH THE TESTICULAR FEMINIZATION SYNDROME
Authors: Ismail A. A. A. , Davidson D. W. , Souka A. R. , Loraine J. A. , Foss G. L.
Published: December 2008

A prolonged study extending over 77 days in a patient with testicular feminization was conducted during which castration was performed and gonadal and adrenal stimulation undertaken. Prior to castration levels of urinary testosterone and epitestosterone were high and cyclic changes in oestrogens and pregnanediol output were not noted. Following operation there was a marked decrease in the excretion of androgenic steroids but no significant changes following HCG administration. The main endocrinological feature of this patient was the lack of cyclicity of gonadal steroids.
COMPARATIVE STUDY OF THREE TESTS FOR THE ASSESSMENT OF HYPOTHALAMIC-PITUITARY-ADRENOCORTICAL FUNCTION
Authors: Angulo M. S. Laurent de , van Gelderen H. H.
Published: December 2008

An attempt has been made to determine the value of the lysine-8-vasopressin test when used together with the insulin-induced hypoglycaemia and the metyrapone test for the differentiation between hypothalamic and pituitary secondary adrenocortical insufficiency. This study was carried out in 65 children and adolescents with various disorders associated with growth retardation or overweight. The criteria for normal responses to the tests were based on findings in a 'control' group consisting of children with short stature without endocrinological disease. These criteria have been discussed in detail.

In the control group, the concordance between the results of each of the tests was good. As far as the groups with proven or possible hypothalamic and/or pituitary disorders were concerned, discrepancies between the LVP test results and those of the ITT were found in a considerably higher proportion of cases. The combination of an abnormal ITT and a normal LVP test was encountered significantly more often than the reverse situation. This is in agreement with the hypothesis that LVP acts directly on the adenohypophysis while ITT acts at the hypothalamic or higher levels. The LVP test seems to be a valuable additionto the tests of hypothalamic-hypophyseal function.
GONADOTROPHINS, TESTOSTERONE AND OESTROGEN LEVELS IN RELATION TO OVARIAN MORPHOLOGY IN 11β-HYDROXYLASE DEFICIENCY
Authors: Sizonenko P. C. , Schindler A. M. , Kohlberg I. J. , Paunier L.
Published: December 2008

Two siblings, aged 6 years 2 months and 4 years 2 months respectively, with the hypertensive form of congenital virilizing adrenal hyperplasia due to 11β-hydroxylase deficiency are presented. The blood levels of FSH were in the pubertal range and the LH levels were low. Testosterone-like-substances (TLS) were in the normal range for adult males; urinary oestrogens were increased and the bone ages were 15 and 13 years. Pubertal development had begun although suppression therapy was never started, as shown by the pubertal levels of FSH, and the rapid increase of both FSH and LH when the adrenal secretion was suppressed. Polycystic ovaries were observed in both cases. The role of testosterone and derivatives as well as of FSH in the development of polycystic ovaries is discussed.
METABOLISM OF 3β-HYDROXY-Δ5- AND 3-OXO-Δ4-C19 AND C21 STEROIDS IN HUMAN LIVER MICROSOMES
Authors: Björkhem Ingemar , Einarsson Kurt , Gustafsson Jan-Åke , Somell Anders
Published: December 2008

The metabolism of [4-14C] dehydroepiandrosterone*, [4-14C] pregnenolone, [4-14C] androstenedione, [4-14C] testosterone and [4-14C] progesterone in microsomal preparations of human liver has been studied.

[4-14C] Dehydroepiandrosterone with NADPH as cofactor gave the following composition of products: 3β,7β-dihydroxy-5-androsten-17-one (about 25%), 3β-hydroxy-5-androstene-7,17-dione (about 25%), 3β,7α-dihydroxy-5-androsten-17-one (about 10%), 3β,17β-dihydroxy-5-androsten16-one (about 10%), 6β-hydroxy-4-androstene-3,17-dione (about 10%), 3β,16α-dihydroxy-5-androsten-17-one (< 5%), 5-androstene-3β,16α,17β-triol (< 5%) and 6α-hydroxy-4-androstene-3,17-dione (< 5%). In addition an unidentified hydroxylated derivative of dehydroepiandrosterone (about 10%) was formed. [4-14C] Dehydroepiandrosterone with NAD as cofactor was converted into androstenedione.

[4-14C] Pregnenolone with NADPH as cofactor was metabolized only to a small degree, and of the products formed, only 6β-hydroxy-4-pregnene-3,20-dione (about 20% of products) and 3β,16α-dihydroxy-5-pregnen-20-one (about 10% of products) could be identified. Pregnenolone with NAD as cofactor was converted into progesterone.

[4-14C] Testosterone with NADPH as cofactor gave the following composition of products: 6β,17β-dihydroxy-4-androsten-3-one (30–50%), androstenedione (25–40%), 2ε,17β-dihydroxy-4-androsten-3-one (5–10%), 6β-hydroxy-4-androstene-3,17-dione (about 5%), 1β,17β-dihydroxy-4-androsten-3-one (< 5%), 15β,17β-dihydroxy-4-androsten-3-one (< 5%) and 16α,17β-dihydroxy-4-androsten-3-one (< 5%).

[4-14C] Androstenedione with NADPH as cofactor gave the following composition of products: 6β-hydroxy-4-androstene-3,17-dione (50–60%), 5α-androstane-3,17-dione (about 10%), testosterone (about 5%), 17β-hydroxy-4-androstene-3,16-dione (about 5%) and 3β-hydroxy-5α-androstan-17-one (about 5%).

[4-14C] Progesterone with NADPH as cofactor gave the following composition of products: 6β-hydroxy-4-pregnene-3,20-dione (about 30%), 5α-pregnane-3,20-dione (10–20%), 3β-hydroxy-5-pregnan-20-one (about 10%) and 6α-hydroxy-4-pregnene-3,20-dione (5%).
IN VIVO UPTAKE AND METABOLISM OF 3H-TESTOSTERONE AND 3H-5α-DIHYDROTESTOSTERONE BY HUMAN BENIGN PROSTATIC HYPERTROPHY
Authors: Becker H. , Kaufmann J. , Klosterhalfen H. , Voigt K. D.
Published: December 2008

Thirty min before prostatectomy, either 400 μCi [1,2-3H] testosterone (51 Ci/mM) or 400 μCi [1,2-3H] 5α-dihydrotestosterone (44 Ci/mM) was injected intravenously into human patients with benign prostatic hypertrophy (bph). Total radioactivity was counted in aliquots of blood, of skeletal muscle, of prostate and of different parts of the prostatic adenomas. After extraction, the unconjugated steroids were isolated by TLC in different systems. The following results were obtained: 1. The endogenous plasma concentrations of testosterone and 5α-dihydrotestosterone (5α-DHT) in patients with bph are within the normal range. 2. Testosterone and 5α-DHT accumulate to a greater extent in prostatic tissue than in muscular tissue. 3. 5α-DHT is the main metabolite in prostatic tissue, the extent of 5α-reduction depending on the predominant type of tissue present. 4. In muscle no 5α-reduction of testosterone occurs, whereas exogenous 5α-DHT is efficiently metabolised to androstanediols and androsterone. 5. The androgen concentrations and the distribution of metabolites in the blood do not reflect the situation in the prostate or in skeletal muscle.
METABOLISM OF DEHYDROEPIANDROSTERONE AND ANDROSTENEDIONE IN A NEWBORN ANENCEPHALIC MONSTER AT TERM
Authors: Benagiano G. , Torre B. de la , Gualtieri R. , Diczfalusy E.
Published: December 2008

A newborn anencephalic monster was injected with carbon-14 labelled dehydroepiandrosterone and tritium labelled androstenedione and metabolites recovered from various tissues and blood specimens were analysed. Dehydroepiandrosterone was readily converted to dehydroepiandrosterone sulphate in all tissues studied. Furthermore, unconjugated as well as conjugated 5-androstene-3β,17β-diol and conjugated 16α-hydroxy-dehydroepiandrosterone were isolated from the liver. Very little, if any, of the injected dehydroepiandrosterone was converted to Δ4-3-ketosteroids, ring A reduction products or oestrogens.

On the other hand, androstenedione was rapidly metabolized to testosterone, a variety of unconjugated and conjugated reduction products and conjugated oestrogens.

From the different tissues, the following unconjugated compounds were isolated in a radiochemically homogenous form: testosterone (liver, blood, kidneys, gastrointestinal tract, lungs, thymus), 5β-androstanedione (liver), 5β-androsterone (liver, blood, kidneys, gastrointestinal tract, lungs, thymus), epi-5β-androsterone (liver), 5β-androstane-3α,17β-diol and 5α-androstanedione (blood, combined extract of all organs), 5α-androsterone (liver, blood, kidneys, gastrointestinal tract, lungs, thymus), 5α-dihydrotestosterone (combined foetal organs except the liver) and epi-5α-androsterone (blood and combined foetal organs except the liver). From the solvolysed conjugated fraction, the following steroids were isolated: 5β-androstane-3α,17β-diol (liver), 5β-androsterone (liver, blood, kidneys, gastrointestinal tract, lungs, thymus), epi-5β-androsterone (liver), 5α-androsterone (liver, blood, kidneys, gastrointestinal tract, lungs, thymus), testosterone (liver, blood, kidneys, gastrointestinal tract, lungs, thymus). The 5β-forms were predominant in the liver, whereas the 5α-forms dominated the pattern in all other tissues studied, including the blood.

The data indicate that the androgen metabolism of the anencephalic monster studied, did not differ qualitatively from that of midterm foetuses.
PERIPHERAL PLASMA LEVELS OF 17α-HYDROXYPROGESTERONE, PROGESTERONE AND OESTRADIOL DURING NORMAL MENSTRUAL CYCLES IN WOMEN
Authors: Holmdahl Tore H:son , Johansson Elof D. B.
Published: December 2008

Liquid-gel chromatography on hydroxyalkoxypropyl Sephadex has been used to separate 17α-hydroxyprogesterone* and progesterone from interfering steroids prior to assay by competitive protein binding. During the luteal phase 0.5 ml of plasma was enough for determinations of both steroids. Fifteen samples could be assayed in less than 48 h. Oestradiol in plasma was assayed by radioimmunoassay. Daily blood samples were collected during 10 normal menstrual cycles in young, healthy women. The average cycle length was 29.7±2.0 (sd) days. 17α-hydroxyprogesterone displayed a midcyclic peak averaging 1.86±0.70 (sd) ng per ml coinciding with a midcyclic peak of oestradiol averaging 16.50± 5.95 (sd) ng per 100 ml of plasma. The highest luteal phase level of 17α-hydroxyprogesterone was 1.94 ±0.72 (sd) ng per ml. The corresponding levels for oestradiol were 9.1 ±3.8 (sd) ng per 100 ml. Progesterone formed a luteal plateau averaging 12.3±2.3 (sd) days. The highest luteal level of progesterone was 14.6±2.1 (sd) ng per ml. The peripheral plasma pattern of 17α-hydroxyprogesterone seems to mimic that of oestradiol during the human menstrual cycle.
PERIPHERAL PLASMA LEVELS OF 17α-HYDROXYPROGESTERONE DURING HUMAN PREGNANCY
Authors: Holmdahl Tore H:son , Johansson Elof D. B.
Published: December 2008

Peripheral plasma levels of 17α-hydroxyprogesterone* were measured during normal human pregnancy. During the first trimester measurements of peripheral plasma progesterone were also included. Five cases of early pregnancies were followed with frequent blood-sampling until the 14th week of gestation. In one of the women daily blood samples were collected from 10 days prior to conception until the beginning of the 6th week. From the 18th week on, a total of 173 blood-samples were obtained from individual patients. During the 7th week the average plasma levels of 17α-hydroxyprogesterone reached a maximum of 3.7 ng per ml followed by a gradual decline. From week 14 to week 34 the mean level was around 0.5 ng per ml. Thereafter an increase towards term was noted with a mean plasma level of 17α-hydroxyprogesterone of about 2 ng per ml in week 40. Peripheral plasma progesterone decreased from a mean level of 27.0 ng per ml in week 5 to reach a nadir of 16.0 ng per ml in weeks 8 and 9 followed by a gradual increase. No correlation between the plasma levels of 17α-hydroxyprogesterone and the clinical outcome of pregnancy could be demonstrated.
DE NOVO SYNTHESIS OF STEROIDS AND STEROID SULPHATES BY THE TESTICLES OF THE HUMAN FOETUS AT MIDGESTATION
Authors: Mathur R. S. , Wiqvist N. , Diczfalusy E.
Published: December 2008

The de novo synthesis of steroids and steroid sulphates by the testicles of four human foetuses at midgestation was studied. Two foetuses and two foeto-placental units were perfused at 36°C for 120 minutes with 3.0 and 6.0 mCi of [14C] sodium acetate, respectively.

Radiochemically homogeneous steroids and steroid sulphates were isolated from the testicular extracts. Tritium labelled internal standards were used in order to assess procedural losses.

No labelled steroids were detected in the testicular extracts in one case. From the testicles of each of the three other foetuses pregnenolone, pregnenolone sulphate, dehydroepiandrosterone, dehydroepiandrosterone sulphate, Δ5-androstenediol and testosterone were isolated. Progesterone and androstenedione were isolated in only one case each. Pregnenolone was found to be the predominant steroid formed.

It is concluded that the testicles of midgestation human foetuses synthesize and secrete testosterone. It is likely that for the synthesis of this testosterone, the foetal testicles utilize preferentially the so-called Δ5-pathway.
PEPTIDASE ACTIVITY IN THE HYPOTHALAMI OF RATS TREATED NEONATALLY WITH OESTROGEN
Authors: Griffiths E. C. , Hooper K. C.
Published: December 2008

The previous paper (Griffiths & Hooper 1973) described the activity of certain hypothalamic peptidases following orchidectomy and testosterone propionate injection, and suggested that changes in enzyme levels may be used as an index of gonadotrophin release in male rats, in a similar way to that previously described for female rats (Griffiths & Hooper 1972a). Using this approach, the effect of neonatally administered oestrogen on the hypothalamus was investigated. The marked increase in supernatant activity in male rats and the equally marked decrease in supernatant activity in female rats, both injected during the critical period of hypothalamic sexual differentiation, are interpreted as indicating decreased LH secretion in males and increased LH secretion in females respectively. It can be concluded that the changes in reproductive function produced by neonatally administered oestrogen are caused by alterations in LH-RF metabolism and that the peptidases in the rat hypothalamus are responsible for this metabolism.
INSULIN ANTIBODY FORMATION
Authors: Andersen O. Ortved
Published: December 2008

Sixty-three patients with diabetes mellitus were treated with a porcine or a bovine insulin preparation, either in solution or in a crystal suspension of protamine-insulin. The amounts of circulating insulin-binding antibodies were periodically determined for up to 3 years. Forty-nine patients developed antibodies during the first 6 to 9 months of treatment. Taking into account the length of insulin treatment and the age of the patients, the amounts of antibodies developed were compared for groups treated with the different insulin preparations. Of the patients treated with insulin in a neutral solution, those who had received bovine insulin developed significantly more antibodies than those treated with porcine insulin. Patients treated with porcine insulin in a neutral solution developed only traces of antibodies. The mean titre was significantly less than for patients treated with porcine insulin in an acid solution or as protamine-insulin. Treatment with porcine protamine-insulin resulted in significantly less antibody formation, provided the patients had received porcine insulin in a neutral solution before the treatment with protamineinsulin. It was shown that as a rule, patients developed antibodies with the same avidity for porcine and bovine insulin, although a few patients treated with porcine or bovine insulin developed antibodies with greatest avidity for bovine insulin.
C21 STEROID METABOLISM AND CONJUGATION IN THE HUMAN PREMATURE NEONATE
Authors: Ducharme Jacques R. , Limal Jean-Marie , Antic Branislava , Sandor Thomas
Published: December 2008

The metabolism and conjugation in vitro of exogenous cortisol, 11-deoxycortisol, corticosterone and pregnenolone by liver, adrenal, kidney, intestine, lung, thymus, spleen and skin tissue preparations of premature and full-term newborn infants were studied. A number of tissues possess the enzymatic capacity to transform cortisol to its major metabolites, while metabolism of 11-deoxycortisol was effected exclusively by adrenal tissue preparations. 6β-Hydroxylation of exogenous cortisol was demonstrated by liver, adrenal and intestinal tissue, the latter being the most active. In the liver, 6β-hydroxylation of cortisol was associated with the "mitochondrial" sediment. The conversion of cortisol to cortisone was effected by all tissue preparations, except perhaps the lung in which it was not characterized, but was most pronounced when kidney or adrenal preparations were used as the source of enzymes. Ring A reduction of cortisol to tetrahydro-metabolites was demonstrated by all tissue preparations with the exception of the thymus. Similarly, all tissue preparations were able to produce glucuronide and sulphate conjugates of cortisol metabolites, though the formation of steroid sulphates was relatively low in all tissues under the present experimental conditions. Glucuro- and sulpho-conjugation was effected more readily when pregnenolone and corticosterone were used as substrate instead of cortisol. It is concluded that conjugation and catabolism of corticosteroids, namely cortisol, corticosterone and pregnenolone in the neonate may be the function of many tissues coordinated by factor(s) presently unknown.
INAPPROPRIATE LACTATION AND AMENORRHOEA: PATHOLOGICAL AND DIAGNOSTIC CONSIDERATIONS
Authors: Gates R. B. , Friesen H. , Samaan N. A.
Published: December 2008

Clinical courses and investigations in 4 patients with inappropriate lactation and amenorrhoea of different aetiologies (pituitary tumour, "empty sella" syndrome, del Castillo syndrome and hypothalamic lesion due to histiocytosis-x disease) are reported. Basal serum immunoreactive prolactin (HPr) was normal in the patient with "empty sella" syndrome but subnormal after intravenous synthetic thyrotrophin releasing hormone (TRH) administration. In the 3 other patients HPr levels at basal and during TRH administration were high. Highly increased serum HPr levels were reduced after trans-sphenoidal removal of a prolactin producing tumour and a normal pregnancy occurred. Clomiphene citrate failed to increase serum luteinizing hormone (LH) levels or oestrogen excretion in the patient with histiocytosis-x disease who had a posterior hypothalamic lesion but intact anterior pituitary. Absent growth hormone (HGH) secretion during stimulation studies was also associated with the posterior hypothalamic lesion.
PITUITARY GONADOTROPHINS AND 17-KETOSTEROIDS IN PATIENTS WITH THE XYY SYNDROME
Authors: Nielsen Johannes , Johnsen Svend G.
Published: December 2008

The urinary excretion of pituitary gonadotrophins and 17-ketosteroids was studied in nine males with karyotype 47,XYY and the serum testosterone in five such patients. We found a comparatively low urinary excretion of pituitary gonadotrophins as well as of dehydroepiandrosterone. The conclusion of the study combined with previous results is, however, that there are no indications of any pronounced abnormality in the urinary excretion of pituitary gonadotrophins or 17-ketosteroids and normal concentrations of serum testosterone in males with the XYY syndrome, in spite of the abnormality of the testis found in a high proportion of such patients.
THE INFLUENCE OF DIPHENYLHYDANTOIN AND CARBAMAZEPINE ON THE CIRCADIAN RHYTHM OF FREE URINARY CORTICOIDS AND ON THE SUPPRESSIBILITY OF THE BASAL AND THE "IMPULSIVE" ACTIVITY BY DEXAMETHASONE
Authors: Köbberling J. , zur Mühlen A. v.
Published: December 2008

In eight normal volunteers the circadian rhythm of cortisol was established by the determination of free urinary corticoids in 2 h urine samples by the competitive protein binding method. After two control days dexamethasone was infused between 10 p. m. and 4 a. m. in doses between 50 and 400 μg/h. These experiments were repeated after pre-treatment with 400 mg diphenylhydantion/day for one week and again after pre-treatment with 800 mg carbamazepine/day.

Under the influence of these anti-convulsant drugs the circadian rhythm of free urinary corticoids was still present but showed more irregularities and sometimes additional peaks in the course of the day. The 24 h excretion values, the peak and the nadir values and the time of the morning peaks were not significantly different from the control days. The degree of suppression by dexamethasone was dose related both with and without the application of the anti-convulsants but under the influence of both these drugs comparable effects could only be achieved by 2 to 4 fold higher doses of dexamethasone. The suppression of basal and impulsive cortisol activities was inhibited in a similar way. According to these results it can be assumed that the anti-convulsants interfere with the feedback mechanism by decreasing the sensitivity of the central nervous system to changes in plasma glucocorticoid concentrations. An intact feedback mechanism does not seem to be an essential condition for the circadian rhythm.
FAMILIAL POLY-ENDOCRINOPATHY
Authors: Frey Harald M. M. , Vogt Jørgen H. , Nerup Jørgen
Published: December 2008

Two family histories are presented. In the first (family W.) two siblings, aged 12 and 16, had idiopathic Addison's disease. The younger patient also had a goitre, possibly representing Hashimoto's thyroiditis. In the second family Graves' disease was present in three generations in direct succession. The oldest patient in addition had Addison's disease, diabetes mellitus and total alopecia. Organ-specific antibodies were looked for quite extensively in the serum of the patients and their relatives, with several positive findings, but without a consistent pattern.

A review is given of the literature on familial poly-endocrinopathies and the probable auto-immune character of these dieases.

The present cases constitute strong evidence for a genetic transmission of these diseases, and for a common basic aetiology. If this common basis is an auto-immuno aberration, it seems most reasonable, in view of the polyglandular involvement, to assume that the immune-system proper is at fault, rather than a defect in the individual organs.
INFLUENCE OF GONADOTROPHINS AND CYCLIC AMP ON CARBOHYDRATE AND PROTEIN METABOLISM IN THE IMMATURE RAT OVARY
Authors: Hamberger Lars , Herlitz Hans , Sjögren Anita
Published: December 2008

Ovaries from rats varying in age between 5–12 days were incubated in Krebs bicarbonate buffer at 37°C containing 5.5 mmol/l glucose. A 2 h incubation in the presence of 0.01 μg/ml LH (NIH-LH-B6) caused an increase in lactic acid production as compared to controls, and a clear dose-response was demonstrated up to 100 μg/ml. In vitro the addition of 100 μg/ml FSH (NIH-FSH-S5) or 10 mmol/l cyclic AMP also caused stimulatory effects on lactate production. In experiments with ovaries from 8–9 day old rats, incubations were carried out in a medium containing 0.1 mmol/l [14C]AIB (α-aminoisobutyric acid), and the distribution ratios for this model amino acid were determined after 2 h incubation in the absence and presence of LH, FSH or cyclic AMP respectively. No hormonal effects were demonstrated, while cyclic AMP caused a significant increase in the [14C]AIB uptake.

In further experiments ovaries from 9 day old rats were incubated in medium containing both [14C]AIB (0.1 mmol/l) and [3H]leucine (0.03 mmol/l). Four hours before the removal and incubation of the ovaries the rats were injected ip with FSH or LH (500 μg/100 g body weight) or saline. The distribution ratios of both [14C]AIB and [3H]leucine were significantly elevated in the FSH injected group while LH was ineffective. In similar experiments with 0.01 mmol/l [3H]proline it was also possible to demonstrate an increased incorporation of this amino acid into ovarian protein after a single FSH injection 2 h before the incubation.
A SIMPLE TECHNIQUE FOR MEASURING THYROXINE SECRETION RATE IN THE MOUSE
Authors: England P. , Webb J. , Harland W. A. , Whaley K.
Published: December 2008

Thyroxine secretion rates in mice may be estimated by a single bleed following injection of a tracer dose of radiothyroxine. Assumptions inherent in the procedure under different experimental conditions are discussed and validated at several environmental temperatures.