bluuebunny/crossref_metadata_2025 huggingface dataset:
SYNTHETIC LH-RH AS A THERAPEUTIC AGENT
Authors: Breckwoldt M. , Czygan P.-J. , Lehmann F. , Bettendorf G.
Published: December 2008

The present paper describes clinical experiments performed in order to study the therapeutic value of synthetic luteinizing hormone-releasing hormone (LH-RH) in patients with anovulatory sterility. The endocrine state of the patients was defined by the following parameters: Total urinary gonadotrophins, total urinary oestrogens, plasma FSH and LH-levels, plasma oestrogens and plasma progestins.

Exclusive administration of 100–200 μg synthetic LH-RH daily for 18–21 days did not result in any ovarian stimulation as determined by plasma oestrogens. HMG-stimulation, however, caused a rapid increase in plasma oestrogen values.

In a group of 13 patients with primary or secondary amenorrhoea LH-RH was used for the induction of ovulation after HMG-stimulation. LH-RH was administered by intravenous infusion at a rate of 50 μg/h for 2–8 hours. The LH increase to the pre-ovulatory levels of 50–88 mU/ml was noted in 8 patients, ovulation, however, presumably occurred in only 4 patients. One patient conceived, but the pregnancy was terminated as early abortion. An additional injection of HCG 4 days after the LH-RH infusion resulted in ovulation in one patient as evidenced by subsequent pregnancy.

The data presented indicate that synthetic LH-RH is not suitable for the induction of ovulation in HMG-stimulated ovaries. The therapeutic value of LH-RH is probably limited by the responsiveness and capacity of the pituitary.
IRREVERSIBLE INHIBITION OF PITUITARY PROLACTIN AND GROWTH HORMONE SECRETION AND OF MAMMARY GLAND DEVELOPMENT IN MICE BY MONOSODIUM GLUTAMATE ADMINISTERED NEONATALLY
Authors: Nagasawa Hiroshi , Yanai Reiko , Kikuyama Sakae
Published: December 2008

A single subcutaneous injection of 4 mg monosodium glutamate (MSG) to neonatal female mice resulted in obesity when the mice became adult. The MSG-treated mice had significantly smaller contents of prolactin and growth hormone (GH) in the pituitary, as compared with the controls at 60, 150 and 420 days of age except for the content of prolactin at 60 days of age. The development of normal and pre-neoplastic mammary systems was markedly suppressed in the MSG-treated mice at 150 and 420 days of age. The oestrous cycles of the MSG-treated mice showed longed periods of oestrus and shorter periods of dioestrus than those of the controls. The pituitary weight was significantly smaller in the MSG-treated mice than in the controls at 60 and 150 days of age. The weights of several other organs showed no difference between the groups at any of the ages examined. These results indicate that MSG inhibits the pituitary secretion of prolactin and GH through its deleterious effects on the hypothalamus and that the effects are irreversible.
BONE MINERAL CONTENT IN PATIENTS WITH PRIMARY HYPERPARATHYROIDISM WITHOUT RADIOLOGICAL EVIDENCE OF SKELETAL CHANGES
Authors: Dalén Nils , Hjern Bo
Published: December 2008

Bone mineral content was determined by X-ray spectrophotometry at 7 sites in 10 patients suffering from primary hyperparathyroidism without any radiological evidence of skeletal alterations. Bone mineral assays were performed before parathyroidectomy and one year after the operation in order to ascertain whether the bone mineral level is abnormal in this disease, and also whether it increases after parathyroidectomy.

In comparison with a control-group of 170 subjects the pre-operative level of bone mineral content was low for the distal radius and ulna and the calcaneus, as was the amount of bone mineral per unit volume of cortical bone in the femoral shaft. After parathyroidectomy, the mean bone mineral content for the series increased significantly in the distal radius and ulna, in the femoral neck and the calcaneus.
GLUCOSE TOLERANCE AND SERUM INSULIN IN RATS AND INSULIN SENSITIVITY OF RAT ADIPOSE CELLS FOLLOWING TREATMENT WITH THE PROGESTOGEN CLOMEGESTONE ACETATE
Authors: Schillinger E. , Gerloff Ch. , Gerhards E. , Günzel P.
Published: December 2008

Daily treatment of rats for 2–4 weeks with 2.5 and 8 mg/kg clomegestone acetate subcutaneously (sc) results in an impairment of the intravenous (iv) glucose tolerance in spite of high circulating insulin concentrations. This effect is associated with reduced sensitivity of adipose tissue cells towards added insulin as measured in glucose conversion to CO2 and in the antilipolytic effect of insulin. In addition, fat cells exhibit a reduced response to the lipolytic action of epinephrine. Serum free fatty acids are not appreciably altered neither in fed nor in starved animals. Glycogen deposition in liver is increased. The implications of the increased insulin levels are discussed.
HYPERCORTICISM IN RABBITS IMMUNIZED AGAINST CORTICOSTEROIDS
Authors: Gless K. H. , Hanka M. , Vecsei P. , Gross F.
Published: December 2008

In rabbits immunized with hemisuccinate-albumin complexes of cortisol, corticosterone, deoxycorticosterone, and aldosterone, or against all 4 corticoids simultaneously, antibody titres and plasma concentrations of the corresponding hormones were measured by means of radioimmunoassay.

In immunized rabbits, plasma concentrations were generally higher than in non-immunized controls. Plasma concentrations of cortisol were above 100 μg/100 ml in the animals with the highest cortisol antibody titres (control below 3.5 μg/100 ml). Plasma corticosterone concentrations reached levels of 20–100 μg/100 ml (control below 3.5 μg/100 ml) in rabbits immunized against corticosterone, deoxycorticosterone, or against all 4 corticoids. Concentrations of aldosterone in rabbits immunized against this hormone were 100–1000 times higher than in the control animals (17.9 ± 3.4 ng/100 ml). In all immunized animals the disappearance of intravenously administered labelled corticoids from plasma was delayed as compared with controls, indicating a diminished plasma clearance rate. After administration of ACTH, plasma concentrations of cortisol and corticosterone were the more elevated, the higher the antibody titre was.

Despite the high antibody titres, immunized animals had no signs of adrenal insufficiency. On the contrary, some of the animals showed symptoms of hypercorticism.

The mechanisms that may be responsible for the elevated plasma concentrations of the various corticoids are discussed.
URINARY EXCRETION OF OESTRONE AND OESTRADIOL-17α IN COWS WITH CYSTIC OVARIES
Authors: Lunaas T. , Refsdal A. O. , Garm O.
Published: December 2008

Using a method comprising fluorimetry the urinary excretion of oestrogens was determined daily for an extended period of time in two cows with ovarian cysts. The excretion patterns were characterized by wide peaks separated by relatively narrow minima spaced over 2–4 weeks. During the repetitive periods of high excretion rates the urinary contents of oestrone as well as of oestradiol-17α were considerably larger than those associated with an ovulatory follicular phase in normal cows.

The oestrogen excretion in the abnormal animals decreased to low levels after ovariectomy which was performed after an observation period of about 10 weeks.
EFFECTS OF NORETHISTERONE ON PITUITARY AND OVARIAN FUNCTION
Authors: Collins W. P. , Koullapis E. N. , Ferguson K M. , Biswas S. , Sharples M. J. , Sommerville I. F.
Published: December 2008

The effect of norethisterone (17α-ethynyl-17β-hydroxy-19-norandrost-4-en-3-one) on certain aspects of pituitary and ovarian function has been investigated in seven healthy women. Twenty-four urine samples were collected daily throughout control cycles and subsequently during the second cycle of treatment with 0.35 mg/day of norethisterone. LH, FSH and total oestrogens were measured in all urine specimens and the level of pregnanediol-3α-glucuronoside on selected days during the luteal phase. In addition, progesterone, 17-hydroxyprogesterone and oestradiol were determined in peripheral venous plasma nine days after the peak of urinary LH. At the same time, progesterone secretion and metabolism were assessed from the analyses of urinary metabolites following the intravenous administration of labelled progesterone.

The results show that, in general, norethisterone at this dose does not affect either the level or pattern of FSH, but in five subjects, there was a variable reduction in the midcycle peak of LH (to 33–85 % of the control value). In six subjects, there was a marked reduction in the levels of urinary pregnanediol (to 8–80% of the control value), plasma progesterone (16–55 %), and the urinary production rate of progesterone (3–51 %). In contrast, the level of urinary oestrogen per cycle was increased to 140–160 % in all subjects and the mean values showed an abnormal cyclical pattern. Changes in the distribution of labelled metabolites during treatment indicated the existence of at least two pools of progesterone metabolism.
IN VITRO EFFECTS OF OESTRADIOL AND PROGESTERONE ON THE NUCLEIC ACID BIOSYNTHESES OF THE HUMAN FULL TERM PLACENTA
Authors: Sarkar G. C. , Mukherjee Geeta
Published: December 2008

The in vitro effects of oestradiol and progesterone on the incorporation of H3 32PO4 into full term placental nucleic acids were studied. Oestradiol in a concentration of 10−6 molar and progesterone in a concentration of 10−5 molar showed optimum placental synthesis of RNA. On the other hand, the presence of a higher concentration of oestradiol than the optimum amount gave an inhibitory effect. In the case of progesterone, both the lower and higher concentrations than the optimum were inhibitory. A synergistic action on placental RNA synthesis was indicated by these hormones at their optimum concentrations. Under these conditions actinomycin D did not affect the placental RNA synthesis, suggesting a possible prevention by these hormones of the attachment of actinomycin D to the DNA chain. The DNA synthesis mechanism of the full term placenta operated at a very low efficiency and was not affected by the hormones.
BIOLOGIC AND BIOCHEMICAL EFFECTS OF ANTI-ANDROGENS ON RAT VENTRAL PROSTATE
Authors: Geller Jack , McCoy Kevin
Published: December 2008

To determine whether the similarity of biologic effects of two antiandrogens, cyproterone acetate (Cyp A) and edogesterone (PH-218), could be related to one or more common biochemical effects, we have compared the effects of both drugs on 3H testosterone (3HT) entry into cells, binding to specific cytosol and nuclear androphiles, and conversion to dihydrotestosterone (DHT). In chronic in vivo studies, both Cyp A and PH-218 reduced rat prostate weights by approximately 50% and specific cytosol steroid-protein complex formation by approximately 60 %. At the same time, Cyp A decreased the formation of nuclear steroid-protein complex to 10% of control values, compared with 40% for PH-218. In addition, Cyp A, but not PH-218, significantly decreased total 3HT uptake by the prostate. Similar effects of Cyp A on 3HT uptake, binding, and metabolism were noted in acute in vivo and in vitro experiments. PH-218 effects on these same parameters were reduced in acute, compared to chronic, studies. Neither drug significantly affected the conversion of T to DHT. Despite quantitative differences between Cyp A and PH-218, these studies support the concept that the biochemical common denominator for the biologic effects of anti-androgens is inhibition of specific steroid-protein complex formation in both cytosol and nucleus.
ACTION OF CYCLIC ADENOSINE 3′,5′ MONOPHOSPHATE ON PROTEIN SYNTHESIS IN A THYROIDAL CELL-FREE SYSTEM. RELATION TO ATP AND GTP
Authors: Wägar Gustav
Published: December 2008

The effect of cAMP was studied in a microsomal cell-free system from bovine thyroid glands at low K+ (18 mm) and Na+ (2.5 mm) concentrations. cAMP (2.5–5.0 mm) caused an inhibition of [14C] leucine incorporation into TCA-precipitable protein. When equimolar concentrations of theophylline were added to the cAMP system stimulation of leucine incorporation was observed. It is suggested that the divergent effects of cAMP and the cAMP-theophylline combination is mainly due to different proportions of intact cAMP and its antimetabolite.

The stimulating effect of 1 mm cAMP-theophylline was detected at ATP concentrations ranging from 1.4 to 3.4 mm and GTP from 0.2 to 1.2 mm. High concentrations of ATP and GTP caused an inhibition, which was similar to that produced by EDTA. The inhibition was probably due to chelation of Mg2+.

The stimulating effect of cAMP-theophylline at 18 mm K+ was no longer visible when the concentration of K+ was increased to 72 mm. The stimulation of 2 mm ATP added to the basic system (1.4 mm ATP) at low K+ concentration was also no longer observed at 72 mm K+.

It is concluded that the cAMP effect is "ATP-like" in some respects.
COMPETITIVE INHIBITION BETWEEN OXYTOCIN AND LUTEINIZING HORMONE-RELEASING FACTOR (LRF) FOR THE SAME ENZYME SYSTEM IN THE RAT HYPOTHALAMUS
Authors: Griffiths E. C. , Hooper K. C.
Published: December 2008

From the observation that hypothalamic peptidases inactivating oxytocin might be involved in luteinizing hormone-releasing factor (LRF) metabolism and that the hypothalamus contains enzymes which can inactivate LRF, competitive inhibition studies were performed to determine if the peptidases inactivating oxytocin could act on LRF. In mixed substrate incubations, LRF significantly decreased peptidase activity in a hypothalamic supernatant fraction whereas thyrotrophin-releasing factor (TRF) had no effect. From kinetic studies, it was found that there was competitive inhibition between the two polypeptides for the same enzymes and that LRF may be true enzyme substrate. The results confirm the previous proposals that the hypothalamic peptidases can inactivate LRF and the possibility of a role for the enzymes in the regulation of reproductive function is suggested.
SOME FACTORS INFLUENCING TRH BIOASSAY IN MICE
Authors: Virkkunen Pekka
Published: December 2008

In a search for optimal conditions for TRH bioassay by the McKenzie method, the effect of dietary iodine, triiodothyronine (T3) and ambient temperature were studied in female mice. Responses to TRH were so sensitive to T3 that even endogenous thyroid hormones interfered with the assay. A low-iodine diet for 2 weeks and an ambient temperature of 7°C for the last 5 days sensitized the mice to TRH. The TRH responses were maximal when 0.1 μg T3 was given 24 h previously with 131I. The smallest detectable dose of TRH was about 1 ng. With this modification the bioassay can detect both TRH and TSH. The responses due to these 2 hormones can be separated by giving different doses of T3 as pretreatment. It is concluded that each laboratory must study its own local conditions for optimal TRH bioassay.
RETINAL STUDIES IN PATIENTS WITH HYPERGLYCAEMIA, HYPOINSULINAEMIA AND HYPERLIPIDAEMIA ASSOCIATED WITH HYPOPITUITARISM
Authors: Samaan N. A. , Ouais S. G.
Published: December 2008

Twenty-four patients who had a 10-year history of hypopituitarism resulting from treated chromophobe adenoma, without known family history of diabetes, were studied during oral glucose tolerance (GTT), arginine infusion, and insulin tolerance (ITT) tests. All patients were receiving thyroid and cortisone replacement. Serum immunoreactive growth hormone (HGH) was subnormal in all patients compared with normal subjects during both arginine infusion and ITT tests (P < 0.001).

Although 9 of this hypopituitary group were diabetic, all patients showed a subnormal peak immunoreactive insulin rise during an arginine infusion test and subnormal insulinogenic index during an oral glucose tolerance test, when compared with normal subjects in the same age range. Fasting plasma triglycerides were elevated in the majority of patients, serum cholesterol in 8 while free fatty acids were high in all patients.

Hyperglycaemia, hypoinsulinaemia, hyperlipidaemia and low growth hormone levels were not associated with any of the clinical signs of vascular disease frequently seen in diabetic patients.
TRIIODOTHYRONINE LEVELS IN PATIENTS WITH EUTHYROID ENDOCRINE EXOPHTHALMOS AND DURING TREATMENT OF THYROTOXICOSIS
Authors: Hesch R. D. , Huefner M. , von zur Mühlen A. , Emrich D.
Published: December 2008

Serum triiodothyronine (T3) concentrations have been measured in 7 patients with euthyroid endocrine exophthalmos and in 8 patients with hyperthyroidism. These results have been assessed in relation to other tests of thyroid function.

The non-suppressibility of euthyroid endocrine exophthalmos is due to elevated endogenous T3 levels and correlated to a negative response of the pituitary gland to TRH.

In hyperthyroid patients who are euthyroid under antithyroid drug therapy, no general correlation of routine laboratory data with T3 levels, suppressibility and TRH response could be found. There is a gap between normal T3 and T4 levels and the restoration of the normal TRH response. A condition is described in which euthyroid patients show thyrotoxic behaviour of the pituitary receptors.
EFFECT OF MATERNAL ATHYREOSIS ON RAT EMBRYOS DURING THE LATE PHASE OF ORGANOGENESIS
Authors: Köhler E. , Wojnorowicz F. , Ehmke W.
Published: December 2008

In order to elucidate the question whether maternal thyroid hormones are necessary for both growth and differentiation processes during the phase of organogenesis, rats were thyroidectomized on day 6 of gestation (under barbiturate anaesthesia) using a stereomicroscope. Two days after the operation a radio-iodine-test was performed which ensured that only athyroid animals were used for the experiments. The results of the studies on the growth kinetics of 11- to 14-day-old rat embryos as well as on the activity of the DNA-dependent RNA polymerases and the α-glycerophosphate oxidase in rat embryos of operated mother animals showed that thyroid hormones are not required for the early stages of development of rats.
EFFECT OF HEPARIN ON INSULIN SECRETION INDUCED BY GLUCOSE IN DOGS
Authors: Orosz L. , Fischer U. , Hommel H. , Fiedler H.
Published: December 2008

In anaesthetized dogs, heparin given intravenously in a dose of 100 IU/kg 10 min before an ivGTT (0.5 g/kg) inhibited glucose-stimulated insulin secretion as measured in portal and peripheral venous blood. Thus glucose assimilation is reduced. However there was a considerable antilipolytic action of the small quantity of secreted insulin as shown by the diminution of FFA concentration.
IN VITRO EVIDENCE FOR A PROGESTERONE AND CORTICOSTEROID BINDING PROTEIN IN THE HUMAN UTERUS
Authors: McGuire J. L. , Bariso C. D. , Fuller B. S.
Published: December 2008

When 3H-progesterone was incubated with the 273 000 g supernatant fraction from human uteri, labelled steroid was bound to a macromolecular component. Concomitant incubation with unlabelled corticosteroids, progesterone, testosterone and oestradiol-17β depressed binding of 3H-progesterone, whereas cholesterol and the synthetic progestins chlormadinone and medroxyprogesterone acetate did not competitively inhibit 3H-progesterone binding. These findings are consistent with the existence of a transcortin-like progesterone binder in uteri of lower species such as the rat, guinea pig and rabbit.
OESTROGEN FORMATION IN HUMAN FOETUSES PERFUSED WITH [14-14C]PROGESTERONE
Authors: Taylor T. , Coutts J. R. T. , Macnaughton M. C.
Published: December 2008

Four human foetuses of 16–20 weeks gestation were perfused via the umbilical vein with blood containing [4-14C]progesterone. Steroids were subsequently extracted from the livers, ovaries, adrenals and perfusates. Oestriol, containing a 14C-label was isolated and characterised from extracts of the livers, and in one case, the perfusate. Androstenedione, testosterone, oestrone and oestradiol were not present in any of the tissues in identifiable amounts.

The results demonstrate that the mid-term foetus, can form oestriol from progesterone independently of placental aromatisation.
SOME PROPERTIES OF ENZYMES INACTIVATING OXYTOCIN IN THE RABBIT BRAIN
Authors: Hooper K. C. , Hopkinson C. R. N.
Published: December 2008

Some properties of enzymes inactivating oxytocin in the rabbit brain have been investigated. Enzymes acting on oxytocin and cystine di β naphthylamide were compared using enzyme inhibitors. The effect of incubation of both whole brain homogenate and supernatant fraction with deamino oxytocin and deamino carba1 oxytocin was also determined. It is concluded that oxytocin is inactivated by enzymes which are neither amino peptidases nor those which require prior reduction of the disulphide bridge. Comparison with data in the literature suggests that the molecule is probably cleaved at a C-terminal position.

The effects of the injection of oestradiol monobenzoate and of various endocrine physiological states on hypothalamic oxytocinase levels were compared with the effects produced on the levels of cystine di β naphthylamidase. The effect of dehydration on hypothalamic supernatant oxytocinase was also determined. The results suggest that there is no correlation between hypothalamic enzymes inactivating oxytocin and those hydrolyzing cystine di β naphthylamide, and that hypothalamic supernatant oxytocinase may be concerned specifically with gonadotrophin feedback control.
EFFECTS OF SYNTHETIC LH/FSH-RELEASING HORMONE (LRH) ON PLASMA LH AND FSH IN AMENORRHOEIC WOMEN
Authors: Rannevik G. , Thorell J.
Published: December 2008

Eight amenorrhoeic women were given 100 μg synthetic LRH (Hoechst) iv and im, respectively, at an interval of 2 weeks. Four of the women received the iv injection first and four the im injection. The urinary excretion of oestrogens and pregnanediol was low and unaltered throughout the test weeks.

The effects of LRH were compared by serial measurements of the plasma LH and FSH during 8 h. The initial response of LH for up to 25 min and that of FSH for up to 60 min were equal whether LRH was given iv or im. The difference appeared later. Four hours after the injection the mean increase of LH to iv injection was 0.5 ng/ml (N. S.), while that to im injection was 1.9 ng/ml (P < 0.01). The corresponding values for FSH were 1.3 (P < 0.05) and 3.2 (P < 0.001).

The effect of LRH administration im was thus found to be larger and more prolonged.
BIOASSAY OF GROWTH HORMONE
Authors: Thorngren K.-G. , Hansson L. I.
Published: December 2008

The longitudinal bone growth of proximal tibia determined by tetracycline in hypophysectomized rats was used for the bioassay of growth hormone. Female Sprague-Dawley rats were hypophysectomized at 60 days of age and after a post-operative control period of 15 days growth hormone (NIH-GH-B16) was given daily for 5 or 10 days followed by a 10 day period after its withdrawal.

A linear log dose-response relation was found for the two administration models with high precision. In the present investigation the longitudinal bone growth was more favourable as a growth parameter for the bioassay of growth hormone than the body weight and the width of the proximal tibial growth plate.
BIOASSAY OF GROWTH HORMONE
Authors: Thorngren K.-G. , Hansson L. I.
Published: December 2008

The growth stimulating effect of growth hormone was determined with tetracycline as intravital marker of the longitudinal bone growth of proximal tibia in female Sprague-Dawley rats hypophysectomized at 60 days of age. After a post-operative control period of 15 days growth hormone (NIH-GH-B16) was given daily for 5 or 10 days followed by a 10 day period after its withdrawal. L-thyroxine was given in association with the growth hormone administration to potentiate the growth stimulation.

A linear log dose-response relation was found for the two administration models with a high precision. The thyroxine-treatment increased the sensitivity of the bioassay. An administration period of 5 days was found sufficient for the bioassay of growth hormone in thyroxine-treated hypophysectomized rats.

Compared with the earlier bioassay methods for growth hormone, the present bioassay is more favourable when all the factors, such as precision, sensitivity, specificity, and administration period are considered.
THE INFLUENCE OF d-TRIIODOTHYRONINE (d-T3) ON THYROTROPHIN SECRETION IN MAN
Authors: Zabransky S. , von zur Mühlen A. , Köbberling ].
Published: December 2008

d-Triiodothyronine (d-T3) is used in the treatment of hyperlipidaemia. To examine the influence of this kind of therapy on thyroid function the effect of various doses of d-T3 on TRH induced TSH release has been studied in 10 male euthyroid subjects. d-T3 was administered orally for 4 days; blood samples were taken on the first day 12 h after the d-T3 dose and then after an additional 12 h and after 4 days. The final sample was taken on the 5th day after 24 h without d-T3. Administration of 31.25 μg of d-T3 reduced the maximum increase of TSH in response to 200 μg TRH iv by 40%; 62.5 and 125 μg of d-T3 did not produce a significantly higher inhibition (50%; 45%). However, after 250 μg of d-T3, the response to a single dose was reduced by 68 %. After 500 μg of d-T3 TRH did not stimulate TSH at all. After 4 days regardless of d-T3 dosage the inhibition was not significantly lower than after 24 h. Prolonging the administration of 500 μg d-T3 over 3 weeks raised PBI to 150% whereas thyroxine fell to 65% of the values before d-T3 administration. In a primary hypothyroid patient the basal TSH secretion was lowered from 63 to 36 μU/ml by a daily dose of 0.5 mg d-T3 for 12 days. This study demonstrates that TSH release is inhibited by small doses of d-T3. This stresses the importance of assessing thyroid function in patients receiving d-T3.
EFFECT OF PARA-CHLOROPHENYLALANINE ON RAT THYROID FUNCTION
Authors: Coleoni Aldo H. , Masini Ana M.
Published: December 2008

Administration of p-chlorophenylalanine (p-CPA), a brain serotonin (5-HT) depleting agent, induced a significant reduction in thyroid function as evaluated by the thyroid/serum ratio, 24 hour 131I uptake uptake and the 131I biological half-life. The iodo-amino acid composition of hydrolyzed thyroid tissue remained unchanged by the drug. The injection of thyrotrophin (TSH) to rats the endogenous TSH of which had previously been blocked with thyroxine, raised the plasma 131I and PB131I levels in both treated and control rats. The brain 5-HT concentration measured 24 hours following the last dose of p-CPA was markedly lowered by 50 mg/kg/day and 100 mg/kg/day. Cardiac 5-HT stores were only slightly depleted, while the thyroid 5-HT content remained unchanged. These results suggest a role of brain 5-HT depletion on the reduction of thyroid function caused by p-CPA. Some possible mechanisms are briefly discussed.
IN VITRO STUDIES OF TESTOSTERONE AND 5α-DIHYDROTESTOSTERONE BINDING IN BENIGN PROSTATIC HYPERTROPHY
Authors: Steins P. , Krieg M. , Hollmann H. J. , Voigt K. D.
Published: December 2008

The cytosol fractions of prostatic adenoma and of the rectus abdominis muscle, together with the respective plasma samples were investigated in 13 patients in order to clarify whether or not there is an androgen receptor in human benign prostatic hypertrophy.

The following methods were used:

High speed ultracentrifugation in a sucrose gradient and agar gel electrophoresis at low temperature, of the 100 000 g supernatants after in vitro incubation with 3H-testosterone, 3H-5α-dihydrotestosterone, and 3H-oestradiol-17β. In parallel experiments the supernatants were heated to 45°C for 1 h before the steroid incubation.

Displacement experiments with a 100–500-fold excess of various cold androgens.

In the supernatants as well as in the plasma samples the total protein concentration was measured by the biuret reaction. The concentration of albumin and of immunoglobulin G (IgG) in the various biological fluids was determined by quantitative immuno diffusion.

After charcoal stripping the binding of testosterone and of 5α-dihydrotestosterone was estimated quantitatively and correlated to the plasma contamination.

By the methods used no physico-chemical differences in the androgen binding properties of plasma and of prostate cytosol were observed. However, in any individual cytosol a higher 5α-DHT binding than could be related to the plasma contamination was obtained. The question therefore remains open, as to whether the augmented 5α-dihydrotestosterone binding relates to a cellular increase of sex hormone binding globulin (SHBG) or to androgen receptors which do not show up clearly under the experimental conditions used.
THE INFLUENCE OF HAEMOGLOBIN-S AND G6PD DEFICIENCY ON THE ACTIVITY OF THE 17β-HYDROXYSTEROID DEHYDROGENASE OF INTACT HUMAN ERYTHROCYTES
Authors: Sogbesan A. O. , Dada O. A. , Adadevoh B. Kwaku
Published: December 2008

The 17β-hydroxysteroid dehydrogenase activity in intact erythrocytes of Nigerian patients, in particular with regard to haemoglobin genotypes and G6PD* activity was studied. The G6PD activity of the erythrocyte did not affect the oxidative transformation of testosterone to androstenedione and of oestradiol to oestrone. The reduction (reverse transformation) was inhibited in G6PD-deficient erythrocytes but this inhibition was offset by the addition of 0.025 m glucose to the incubation medium. The per cent oxidation transformation of testosterone was higher in Hb-AA than in Hb-SS erythrocytes. It is suggested that the differences may be a result of either lower enzyme activity in the Hb-SS erythrocytes or of differences in the uptake and possibly binding of sex steroids by intact Hb-SS and Hb-AA erythrocytes.
SEX STEROIDS STIMULATE THE ACTIVITY OF HYPOTHALAMIC ARYLAMIDASES IN THE RAT
Authors: Kuhl Herbert , Rosniatowski Christian , Oen Siang-An , Taubert Hans-Dieter
Published: December 2008

The effect of steroid treatment on the activity of hypothalamic arylamidases in male and female rats was investigated. A new and improved method for the assay of arylamidase activity utilizing L-α-amino acid-p-nitroanilides as substrates is presented. The influence of varying experimental conditions on the activity of hypothalamic arylamidases hydrolyzing the p-nitroanilides of cystine, glutamic acid, alanine, tyrosine, leucine, and phenylalanine, such as changes of substrate and enzyme concentration, temperature, incubation time, and pH, were tested. There was a sex-dependent response in the activity of hypothalamic arylamidases to treatment of the rats with sex steroids. In female rats, the injection of 7 μg of ethinyloestradiol was followed 16 hours later by a significant rise of L-cystine and L-glutamic acid arylamidase activity. In male rats, the injection of testosterone and of ethinyloestradiol respectively brought about a general stimulation of all enzyme activities. This indicates that this enzyme system of the male and female rat hypothalamus responds to steroid treatment of the animals with a sex-specific pattern.
BIOASSAY OF GROWTH HORMONE AND PROLACTIN PREPARATIONS BY DETERMINATION OF LONGITUDINAL BONE GROWTH WITH TETRACYCLINE
Authors: Thorngren K.-G. , Hansson L. I.
Published: December 2008

The growth stimulating effect of different growth hormone and prolactin preparations on the longitudinal bone growth in thyroxine-treated hypophysectomized rats was determined by the tetracycline method. The effect of the hormone preparations was compared with that of the 1st International Standard for growth hormone.

The potency calculation showed that the tested human growth hormone preparations have a higher potency than the bovine, ovine and porcine growth hormone preparations. Also potency differences were found between hormones from the same species but prepared by different methods. The prolactin preparations have a considerably lower growth promoting activity than the growth hormone preparations.

The bioassay method used in the present investigation has a favourable mean precision (λ = 0.172) and sensitivity compared with the earlier bioassay methods. The present method increases the possibility of determining the biological effects of various growth promoting substances.
PITUITARY ADENOMA ASSOCIATED WITH INAPPROPRIATE ANTIDIURETIC HORMONE SECRETION
Authors: Greiss Kamal C. , Moses Arnold M. , Krieger Dorothy T.
Published: December 2008

A 50 year old male with a chromophobe adenoma with suprasellar extension manifested hyponatraemia, plasma hypoosmolality, renal salt wasting and inability to excrete dilute urine after a standard water load. The patient exhibited no evidence of thyroid or adrenal insufficiency. The inability to excrete a water load was not corrected by prior cortisone administration but was partially corrected after ethanol ingestion. A measurable inappropriate amount of arginine vasopressin was excreted in the presence of sustained hydration. It is suggested that inappropriate production of antidiuretic hormone either by the adenoma, or secondary to hypothalamic involvement by the suprasellar extension of the tumour was responsible for the observed findings.
QUANTITATIVE STUDIES OF IODINE METABOLISM IN SPORADIC, NON-TOXIC GOITRE
Authors: Agerbæk H. , Jensen S. E.
Published: December 2008

In 129 patients with non-toxic goitre and 27 normal controls, thyroid dynamic patterns were estimated in an attempt to elucidate pathogenesis. The clinically euthyroid state was confirmed by measurement of PBI, T3-sephadex uptake and BMR.

Thyroid clearance (th. cl.), plasma iodide (PII), and absolute iodine uptake (AIU) were determined and a perchlorate discharge test performed. Twenty patients (16%) had a high AIU and were thus suspected of having dyshormonogenesis; nine were thoroughly investigated and in six dyshormonogenesis was found. Both normals and non-toxic goitre patients had a low PII, but in the goitrous patients values were lowest. The thyroid clearance of iodide was significantly higher in the goitre patients, suggesting iodine deficiency to be a major aetiologic factor for goitre formation. AIU was higher in the goitre patients than in normals, suggesting a larger iodine leakage from the thyroid in these patients.
THE "EFFECTIVE THYROXINE RATIO" – NEW IN VITRO TEST OF THYROID FUNCTION AND ITS CORRELATION WITH FREE THYROXINE
Authors: Nauman Janusz , Nauman Alicja
Published: December 2008

The effective thyroxine ratio (ETR) and absolute concentration of free thyroxine (AFT4) were estimated in the sera of 31 normal subjects, 27 hyperthyroid patients, 12 hypothyroid patients and 21 euthyroid pregnant women.

The mean ETR value in the controls was 1.0 ± 0.18, in the hyperthyroid patients 1.31 ± 0.25, in the hypothyroid patients 0.71 ± 0.21 and in normal pregnant women 0.99 ± 0.24. The mean AFT4 in the normal subjects was 3.0 ± 0.53 ng/100 ml, in the hyperthyroid patients 9.49 ± 2.44 ng/ 100 ml, in the hypothyroid patients 0.58 ± 0.15 ng/100 ml and in the pregnant women 2.84 ± 0.63 ng/100 ml, respectively. High reproducibility of ETR and a significant positive correlation between ETR and AFT4 with r = 0.96 suggest that ETR might be a suitable in vitro test for routine clinical evaluation of the thyrometabolic state.
EFFECTS OF HYPOPHYSECTOMY WITH OR WITHOUT ACTH MAINTENANCE THERAPY ON THE FINAL STEPS OF ALDOSTERONE BIOSYNTHESIS IN THE RAT
Authors: Baumann Klaus , Müller Jürg
Published: December 2008

The effects of hypophysectomy, low-dose ACTH administration or both on aldosterone biosynthesis by incubated adrenal tissue were studied in rats during different dietary regimens. Six days after hypophysectomy without any replacement therapy, the capsular adrenals of rats receiving a complete diet converted tritiated corticosterone to aldosterone and 18-hydroxycorticosterone at a normal and at a moderately increased rate, respectively, and produced normal amounts of aldosterone from endogenous precursors. Hypophysectomy, with ACTH maintenance therapy, resulted in significant decreases in these parameters. In rats kept on a sodium-deficient diet, hypophysectomy alone did not alter the conversion rates, but led to a decreased output of endogenous aldosterone. ACTH treatment of intact as well as of hypophysectomized sodium-restricted animals was followed by a decreased incorporation of tritiated corticosterone into aldosterone and 18-hydroxycorticosterone. In rats kept on a potassium-deficient diet, hypophysectomy induced an 800 % increase in the capsular adrenal conversion of added corticosterone to aldosterone and 18-hydroxycorticosterone; this was partially prevented by ACTH treatment. Hypophysectomy with or without ACTH treatment did not impair restoration to the normal of the apparent capsular adrenal 18-hydroxylase activity in response to resumed potassium intake by potassium-restricted rats.

These results indicate that neither the maintenance nor the induction of an increased activity of the enzymes involved in the final steps of aldosterone biosynthesis due to sodium restriction or to an increased potassium intake, depend on a functioning pituitary gland. On the other hand, even small doses of exogenous ACTH, which are just sufficient for the maintenance of a normal adrenal weight in hypophysectomized animals, can cause significant decreases in the activity of these enzymes.
HORMONE AND ENZYME ASSAYS IN PREGNANCY
Authors: Christensen Arne
Published: December 2008

The cystine-aminopeptidase (CAP)1) activity of placental origin (P-CAP) and of tissue origin (T-CAP) has been investigated in plasma from non-pregnant women, during normal pregnancy, in pregnancies complicated with severe pre-eclampsia and in plasma from the umbilical cord. In plasma from non-pregnant women the enzyme activity was significantly higher at pH 5.8 (T-CAP) than at pH 7.65 (P-CAP). During the pregnancy a gradual increase in both T-CAP and P-CAP took place. However, from about day 220 in the pregnancy the P-CAP became higher than the T-CAP.

Between normal pregnancy and pregnancies complicated with severe pre-eclampsia there was only a low significant difference in the T-CAP activity, but highly significant difference in the P-CAP activity.

The normal P-CAP pattern showed a gradual increase from about the 100th to the 270th day. A great spread in normal values was seen especially from about day 238 of gestation, due to variations in the enzyme activity of the women.

The coefficient of correlation between the P-CAP and the crude placental weight was calculated to + 0.67.

The half-life of P-CAP was calculated to 8.3 days.

In plasma from the umbilical cord the T-CAP activity was significantly higher than the P-CAP, and was simultan that in plasma from non-pregnant women.
CONTROL OF PITUITARY FSH IN MALE RATS
Authors: Steinberger Emil , Chowdhury Mridula
Published: December 2008

The pituitary and serum FSH levels were measured in cryptorchid or orchiectomized adult rats at time intervals up to 7 days after surgery utilizing a radioimmunoassay technique. In orchiectomized rats the pituitary levels showed a decline during the first 72 hours after surgery while serum levels showed an increase during this period of time. Between the 3rd and 7th days after surgery the serum levels remained elevated and pituitary levels depressed. In cryptorchid animals the pituitary levels showed marked rise during the first 72 hours after surgery and remained elevated until the end of the experiment. The serum levels showed no change during the first 72 hours and a slight elevation by 7 days. Administration of testosterone propionate (TP) prevented the ochiectomyinduced changes in pituitary and plasma FSH levels. A dose relationship was observed between the serum FSH levels and the dose of TP. With increase in TP dose up to 0.5 mg an increase in pituitary FSH levels was observed. Further increase in TP dose caused a drop in pituitary FSH levels. The plasma levels showed a progressive drop with increasing doses of TP. The data reported in this paper and information available in literature lead the authors to the conclusion that testosterone regulates primarily FSH release rather than its synthesis.
THE IMMEDIATE RESPONSE OF THE PLASMA PROLACTIN LEVEL TO OESTROGEN AND PROGESTERONE INFUSIONS IN BULLS
Authors: Schams D. , Reinhardt V. , Karg H.
Published: December 2008

The technique of radioimmunoassay was used to determine prolactin concentration in plasma taken from bulls during and after infusions of oestradiol-17β and progesterone. During the infusion of oestradiol-17β (0.5, 1 and 2 mg) for 1 h the concentration of prolactin in the plasma fell, but showed an immediate increase of up to 6-fold after the infusion was completed. A dose-dependent increase (up to 20-fold) in prolactin concentration was observed after the infusion for 1 h of 5, 10, 40 and 80 mg progesterone. In those experiments in which 40 and 80 mg were administered the depression normally seen during the infusion was sustained for 2–3 h and the subsequent increase during the next few hours was comparatively small.
A NEW IN VITRO METHOD FOR ASSAY OF THE BIOLOGICAL ACTIVITY OF GROWTH HORMONE
Authors: Saxena R. K. , Talwar G. P.
Published: December 2008

An in vitro method for the assay of the biological activity of growth hormone is described. The method is based on the stimulation by the hormone of the incorporation of radioactive uridine into RNA in thymocytes from young rats. The response is dose-dependent and is linearly proportional to the concentration of growth hormone up to 16 μg/ml. Other pituitary hormones like FSH, LH, ACTH, TSH and oxytocin do not interfere with the assay system. Prolactin has some effect, which is, however, not additive to that of growth hormone. Various parameters of the procedure have been standardized. The index of precision of the method has been calculated to be about 0.05.
EFFECT OF LITHIUM ON DEIODINATING ACTIVITY OF VARIOUS RAT TISSUES IN VITRO
Authors: Männistö P. T.
Published: December 2008

The effect of lithium chloride (LiCl) on the deiodination of iodotyrosines, on the degradation of 125I-L-thyroxine (125I-L-T4) in vitro and on the disappearance of exogenous 125I-L4 and 125I-rat-TSH in vivo was studied in rats.

Iodotyrosine deiodination was studied in vitro with three techniques. The whole thyroid lobes were not satisfactory as substrate. When a diluted mixture of prelabelled iodo-amino acids was used as substrate, thyroid homogenates deiodinated iodotyrosines. The reaction was inhibited by boiling and by 3,5-dinitro-L-tyrosine (DNT), but LiCl (2 × 10−2 m) had no effect. When 125I-3-iodo-L-tyrosine (125I-L-MIT) served as substrate, increasing concentrations of thyroid homogenates showed an increasing deicdinating activity, which was stimulated by NADP (1.5 × 10−4 m). Inhibitors of dehalogenase DNT (10−4 and 10 −3 m) and menandione (10−4 m) inhibited deiodination, but LiCl (5×10−3 − 0.1 m) was again without effect. The degradation of 125I-L-T4 by liver and kidney homogenates was inhibited by LiCl (5 × 10−3 − 0.1 m).

The disappearance of 125I-L-T4 was studied in rats treated with LiCl for 1 – 4 or 60 – 64 days in vivo. The half-lives were as follows: at 1 –4 days, the control rats 15.9 ± 1.3 h and the LiCl treated rats 19.1 ± 2.1 h (P < 0.05) and at 60 – 64 days 11.2 ± 2.0 h and 66.8 ± 12.3 h (P < respectively. The prolonged half-life in the LiCl treated rats was not due to the decreased excretion of radioactivity in the urine or faeces. The biological half-life of 125I-rat-TSH (11.4 ± 3.2 min) was not modified by LiCl treatment for 5 days.

It can be concluded that the antithyroid effect of LiCl neither originates from the inhibition of iodotyrosine deiodination nor from the change in the half-life of TSH. The half-life of thyroxine is prolonged by LiCl, an effect which is perhaps due to the decreased degradation of thyroxine by tissues.
IMPAIRMENT OF INDUCTION OF GLYCOLYTIC ENZYMES AND DEVELOPMENT OF INSULIN RESISTANCE IN RATS AS A RESULT OF CONTINUOUS INSULIN TREATMENT
Authors: Salganik R. I. , Mertvetsov N. P. , Gordienko O. E. , Chesnokov V. N. , Semenova L. A.
Published: December 2008

It has been established that the administration of insulin to rats for 10 days results in a considerable increase of RNA synthesis as well as in the activity of hexokinase and pyruvate kinase in liver cells. Electron microscopic studies have shown that on the 6th day of insulin treatment the size of hepatocytes nucleoli and the number of free ribosomes increase. Moreover on the 10th day of treatment the glycogen content is changed in the liver cells. Following long-term insulin treatment (16–20 days) the liver cells lose their capacity to respond by enhanced RNA synthesis and by the induction of hexokinase and pyruvate kinase.

It has also been demonstrated that insulin administration for 10–15 days significantly decreases blood sugar. However, continuous insulin treatment (up to 25-27 days) elevates blood sugar to values surpassing even the normal value on day 27 of treatment.

The administration of insulin to rats for 25–27 days leads to a decreased tolerance to glucose load. The content of immunoreactive insulin in the blood plasma increases considerably on day 10 of insulin injection and continues to rise more sharply on subsequent days of treatment.
CONTROL OF RAT TESTICULAR MONOAMINE OXIDASE (MAO) ACTIVITY: HYPOPHYSECTOMY, ADRENALECTOMY, FSH, LH. PROLACTIN, HCG AND TESTOSTERONE
Authors: Urry Ronald L. , Frehn John L. , Ellis LeGrande C.
Published: December 2008

Testicular monoamine oxidase activity (MAO) was measured in rats subjected to adrenalectomy, hypophysectomy, or hypophysectomy and treatment with either HCG, FSH, LH, prolactin, or a combination of FSH, LH, and prolactin. Total testicular MAO activity was reduced by hypophysectomy, but unchanged by adrenalectomy. The specific activity of MAO, expressed as units of activity per mg of tissue, increased after hypophysectomy, suggesting that this enzyme is located in a non-germinal-type cell in the testis. In the mature animals total MAO activity decreased during the first 4 weeks and then increased to near normal levels 2 weeks later. Specific activity of MAO increased the first 7 weeks after surgery in immature animals and for 6 weeks for mature animals. In immature animals the specific activity of MAO had regressed to the control level by 15 weeks after surgery. FSH was more effective in increasing total MAO activity, but LH in high concentrations may be capable of increasing it. Additions of 2 or 5 IU of FSH to seminiferous tubules in organ culture also increased MAO activity. Treatment of hypophysectomized animals with HCG or a combination of FSH, LH, and prolactin increased testicular weights and androgen synthesis, but depressed specific MAO activity. Thus, androgens do not appear to increase total MAO activity, but could depress it especially at high concentrations. Injections of pargyline, a MAO inhibitor, significantly increased endogenous serotonin concentrations in rat testes.
THE EFFECT OF NANDROLONE PHENYLPROPIONATE ON 14C-LEUCINE INCORPORATION INTO MUSCLE PROTEIN IN THE RAT AND RABBIT IN VIVO
Authors: Bresloff P. , Fox P. K. , Sim A. W. , der Vies J. van
Published: December 2008

Investigations have been carried out into the incorporation of 14C-leucine into muscle protein of rats and rabbits and its modification by various treatments. Significant decreases in the rate of incorporation of 14C-leucine into protein of the gastrocnemius and levator ani muscles of rats have been observed following hypophysectomy, fasting or treatment with a corticosteroid. In these situations, treatment with an anabolic steroid, nandrolone phenylpropionate, always prevented or reversed the decrease in 14C-leucine incorporation in the levator ani muscle but never in the gastrocnemius muscle.

In contrast to the situation in the rat, the decreased incorporation of 14C-leucine in the gastrocnemius muscle of the rabbit following corticosteroid administration could be partially reversed by the anabolic steroid.

The results demonstrate that 14C-leucine incorporation into muscle protein in vivo following various experimental treatments may vary markedly not only from one species to another but also from one muscle to another. Great care should be taken in interpreting the effect, or lack of effect, of androgenic/anabolic steroids on the basis of the response of a single muscle.