bluuebunny/crossref_metadata_2025 huggingface dataset:
MAMMARY GLAND PROLACTIN RECEPTOR AND PITUITARY PROLACTIN SECRETION IN LACTATING MICE WITH DIFFERENT LACTATIONAL PERFORMANCE
Authors: Nagasawa Hiroshi , Yanai Reiko
Published: December 2008

SHN female mice, a high mammary tumour strain, are superior to SLN, a low mammary tumour strain, in lactational performance. Mammary gland prolactin receptor and pituitary prolactin secretion during lactation were compared between these strains. The binding activity, the number of receptor sites per mg tissue and the association constant were measured by the in vitro incubation of mammary gland slices with 125I-labelled bovine prolactin, and the pituitary and plasma levels of prolactin were assayed by homologous radioimmunoassay. There was only a slight difference between strains in any of the parameters for prolactin receptor and for prolactin secretion on either day 4 or day 9 of the first lactation. Almost all the correlation coefficients between each parameter for prolactin receptor and the pituitary or plasma level of prolactin were not statistically significant. These findings suggest that any parameter for prolactin examined in this study is not always directly indicative of lactational performance and further show that the individual variation in the pituitary prolactin secretion during lactation is not so great as to alter the prolactin receptor.
THE EFFECT OF ACTH AND HCG ON ADRENAL STEROIDOGENESIS IN THE NEONATAL BABOON (PAPIO PAPIO)
Authors: Pepe Gerald J. , Townsley John D.
Published: December 2008

We have studied three, term newborn baboons (Papio papio) to determine whether differential responses to chorionic gonadotrophin (HCG) and ACTH exist with respect to cortisol (F), dehydroepiandrosterone (D), or dehydroepiandrosterone sulphate (DS) secretion as judged by the serum level of these hormones. Serum F, D and DS levels were measured by radioimmunoassay 30, 15 and 0 min prior to constant iv infusion (120 min) of (A) 12 IU ACTH, (B) 2000 USP Units HCG or (C) normal saline. Steroid concentrations measured on samples obtained during the infusion (30, 60 and 120 min) were averaged and compared with the average pre-treatment values. Statistical analyses were by analysis of variance with comparison of individual means by least significant difference procedure. Each animal was examined 6 times (day 1, 2, 3, 7, 8, 9 of life) receiving each treatment twice in a staggered schedule. Mean serum concentrations (μg/100 ml ± sd) of D, DS and F prior to treatment were 8.0 ± 3.8; 394 ± 196; 47.0 ± 18.7, respectively. ACTH, but not HCG, increased (P < 0.025) serum D, DS and F levels. The response of D and F to ACTH expressed as a per cent of pre-treatment values were similar #$x2266; 100 %) and greater (P < 0.05) than the mean DS percentage (29%) response. These results indicate that ACTH but not HCG is an adrenocorticotrophin in the baboon neonate.

Since the effect of ACTH was not limited to C21 steroid hormone production, these results do not support the suggestion that the neonatal baboon adrenal exhibits a differential response to ACTH stimulation.
FAT CELL SIZE AND LIPID CONTENT OF SUBCUTANEOUS TISSUE IN CONGENITAL GENERALIZED LIPODYSTROPHY
Authors: Rognum Torleiv Ole , Bjerve Kristian S. , Seip Martin , Trygstad Olav , Oseid Svein
Published: December 2008

Fat cell size and lipid composition of subcutaneous tissue from 3 patients with congenital generalized lipodystrophy have been measured before and after treatment with either pimozide, fenfluramine or hypophysectomy. The fat cell volume before treatment ranged between 9.8 × 104 and 17.7 × 104 μm3, compared to 9.0 ×104 and 85.3 × 104 μm3 in 15 controls. The amount of lipids was only 1/10 to 1/50 of normal, triglycerides being the most heavily reduced lipid component.

Neither the fat cell size nor the lipid content were affected by treatment with hypophysectomy, pimozide or fenfluramine.
THE INTERNATIONAL REFERENCE PREPARATION OF HUMAN PITUITARY LUTEINIZING HORMONE, FOR IMMUNOASSAY
Authors: Storring P. L. , Bangham D. R. , Cotes P. Mary , Gaines Rose E. , Jeffcoate S. L.
Published: December 2008

The preparation and nature of the International Reference Preparation of Human Pituitary Luteinizing Hormone for Immunoassay are described.

A collaborative assay of this material (coded 68/40) in terms of the International Reference Preparation of Human Pituitary Gonadotrophins (FSH and LH (ICSH)), for Bioassay (coded 69/104) was carried out by twelve laboratories in seven different countries, using different bioassay and immunoassay methods. The weighted combined potency estimate (with 95 % confidence limits) was 52.1 (46.3–58.7) IU/ampoule with male accessory reproductive organ weight gain assays; 80.2 (73.2–87.9) IU/ampoule with ovarian ascorbate depletion assays; 127 (124–129) IU/ampoule with in vitro Leydig cell testosterone production assays; and 124 (121–126) IU/ampoule with testis receptor binding assays. Immunoassay estimates in terms of the same standard were heterogeneous and gave an unweighted mean potency estimate of 33.2 IU with 95% confidence limits of 14.8– 74.4 IU/ampoule.

Estimates from different methods gave significantly different results, and the reasons for this are discussed in terms of the differences between the materials being compared and the methods used in the comparison. These data illustrate the conceptual difficulties involved in comparing hetero geneous reference preparations, especially by both bioassay and immunoassay, and some of the causes of inevitable discontinuity of assay results, as described in the 26th Report of the WHO Expert Committee on Biological Standardization. On the basis of these results, and in the interest of maintaining continuity of its unitage, the International Reference Preparation has been allocated a potency of 77 IU/ampoule.
SERUM GONADOTROPHINS IN RATS AFTER CASTRATION OR HEAT TREATMENT OF THE TESTES
Authors: Aafjes J. H. , Vreeburg J. T. M. , Schenck P. E.
Published: December 2008

In rats spermatogenesis was disturbed by heat treatment of the testes. This resulted in increases of both LH and FSH. The increased gonadotrophin levels could be suppressed with testosterone. For suppression of FSH to levels of control animals more testosterone was needed than for LH.

The increase of gonadotrophins after castration could be suppressed with testosterone released evenly from silastic capsules. For this suppression low serum levels of testosterone relative to testosterone levels in intact control animals were sufficient. This may indicate that testosterone episodically secreted has a lesser suppressive action on gonadotrophin secretion than a constant presence of this hormone.

The suppressive action of testosterone on serum gonadotrophin levels after castration was potentiated by 1,4,6-androstatriene-3,17-dione, a steroid which inhibits strongly the enzymatic transformation of testosterone into oestradiol.
THE STABILITY OF STANDARDS FOR RADIOIMMUNOASSAY OF HUMAN TSH: RESEARCH STANDARD A AND THE INTERNATIONAL REFERENCE PREPARATION INITIALLY 68/38
Authors: Cotes P. Mary , Das Rose E. Gaines , Kirkwood T. B. L. , Bennie J. G. , Hunter W. M.
Published: December 2008

The stability of the International Reference Preparation of human TSH for immunoassay (previously distributed in ampoules coded 68/38) and of Research Standard A for HTSH has been examined by radioimmunoassay of accelerated degradation samples (stored as the dry ampouled preparations). Potency estimates on degradation samples suggest a high order of stability of immunopotency recognisable by two antisera (MRC 72/356 and Hunter 3A). For the International Reference Preparation the loss of immunopotency during storage at −20°C is predicted to have been 0.56 % per year.
THYROID HORMONE UPTAKE AND T4 DERIVED T3 FORMATION IN DIFFERENT SKELETAL MUSCLE TYPES OF NORMAL AND HYPERTHYROID RATS
Authors: van Hardeveld C. , Kassenaar A. A. H.
Published: December 2008

In this study hind-limb perfusion was used to investigate conversion of T4 to T3 in skeletal muscle tissue. For this purpose the rats were depleted of thyroid hormones by thyroid ablation with 0.75 mCi 131I and were perfused 2 weeks later, when the skeletal muscle tissue consumed oxygen at a normal rate due to one subcutaneous dose of 10 μg T3/100 g b. w. 3 days before the perfusion experiments were started. T4*1) of high specific activity (> 2000 μCi/μg) was added to the perfusate. In the muscle (mixed type) a mean T4 → T3 conversion of 2 % (range 0.5–3.9) was found after 120 min of perfusion. T3 generation from T4 in skeletal muscle did not correspond with T3 muscle uptake. This observation makes a significant overestimation of T3 by selective uptake of a small contamination of T3* in the T4* preparation highly improbable. In red muscle the T4 and T3 uptake was about 50 % higher than in white muscle. The observed Tetracc and T3c were significantly higher in red than in white muscle. The uptake of thyroid hormones by both muscle types was not changed in hyperthyroid rats. The Tetrac and T3 formation from T4, however, was increased in red muscles of hyperthyroid rats. The results show that thyroid hormone metabolism can vary markedly depending upon the type of muscle studied and they present a basis for a better understanding of clinical and biochemical evidence for a different susceptibility of red and white muscle fibers to thyroid hormones.
THYROID FUNCTION DURING PREGNANCY WITH SPECIAL REFERENCE TO HYDATIDIFORM MOLE AND HYPEREMESIS
Authors: Bruun Th. , Kristoffersen K.
Published: December 2008

The thyroid function tests, serum protein-bound iodine (PBI), serum triiodothyronine reaction (T3-test) and serum cholesterol were measured in three groups of pregnant women:

1) 57 with normal pregnancy,

2) 35 with hyperemesis and

3) 14 with hydatidiform mole.

A pattern of high values of PBI and T3-test and relatively low values of cholesterol in most of the patients with hydatidiform mole, and in almost one third of the patients with hyperemesis was found. A positive correlation of the volume of molar tissue and the values of PBI was observed. The treatment of patients with hyperemesis mostly resulted in normalisation of the thyroid function tests, while this was not the case in patients with mole. It is suggested that there might be a common cause of the thyroid stimulation in patients with mole and hyperemesis.
ENDOCRINE EFFECTS OF LITHIUM:
Authors: Christiansen C. , Baastrup P. C. , Lindgreen P. , Transbøl I.
Published: December 2008

Ninety-six manic-depressive patients were studied during long-term lithium treatment. Highly significant elevations were observed respecting the levels of serum immunoreactive parathyroid hormone (P < 0.001) as well as the protein-corrected levels of serum calcium (P < 0.001) and serum magnesium (P <0.001), thus indicating a state of 'primary' hyperparathyroidism. The patients as a group had normophosphataemia and normophosphatasia supporting the impression of a rather mild state of biochemical hyperparathyroidism.
EFFECT OF FASTING ON 32P TRANSLOCATIONS IN PRE-LABELLED PANCREATIC ISLETS
Authors: Asplund Kjell , Freinkel Norbert
Published: December 2008

The rapid, short-lived efflux of inorganic 32P-orthophosphate that occurs when pre-labelled pancreatic islets are exposed to nutrient insulin secretagogues (the "phosphate flush") has been proposed to reflect some early step in β-cell secretory activation. In the present study, glucose-initiated phosphate efflux was studied during fasting.

Pancreatic islets were isolated from fed and 48-h fasted rats by collagenase digestion. After pre-labelling with 32P-orthophosphate and basal perifusion with 0.5 mg/ml glucose, tissue analyses disclosed similar stores of radioactivity in the two groups of islets. Stimulatory perifusion with glucose at this time failed to promote insulin release from islets which had been secured from fasted donors although the "phosphate flush" was preserved. However, the characteristics of phosphate efflux were altered. Maximal glucose-induced phosphate release was greater with islets from fasted animals whereas phosphate release in response to low level stimulation with glucose was diminished. Accordingly, the dose-response curve for glucose-initiated phosphate efflux in islets from fasted rats was displaced to the right and compatible with a decreased sensitivity to glucose at the activation site for the "phosphate flush."

Thus, while glucose is unable to enhance insulin release in vitro after fasting, glucose still elicits increased phosphate efflux. However, the phenomenon appears to be attended by an impaired responsiveness to activation by glucose, supporting the contention that some early step in the sequence of stimulus secretion coupling in the β-cell may be obtunded after food deprivation.
THE EFFECT OF OOPHORECTOMY ON PLASMA OESTRONE AND ANDROSTENEDIONE LEVELS IN THE RAT
Authors: Fearnley M. , Hodgkinson A. , Holmes A. L. , Nordin B. E. C.
Published: December 2008

Plasma oestrone and androstenedione levels have been measured in oophorectomized and sham-operated rats by means of radioimmunoassay. The mean oestrone level in the oophorectomized animals was approximately two-thirds of that in the intact animals while the androstendione levels were about half of those in the intact rats. A direct relationship was observed between the plasma oestrone and androstenedione levels in the control animals and to a lesser extent in the oophorectomized animals. The results indicate that approximately 50 % of circulating androstenedione and 30 % of circulating oestrone originate in the ovaries in the female adult rat.
ENDOCRINE EFFECTS OF LITHIUM
Authors: Transbøl I. , Christiansen C. , Baastrup P. C. , Nielsen M. Damkjœr , Giese J.
Published: December 2008

Hypermagnesaemia is a well-known but as yet unexplained concomitant of lithium treatment. Prior suggestions implicating a role for aldosterone in magnesium homoeostasis prompted this study of plasma renin, plasma aldosterone and serum magnesium in 17 maniodepressive patients on long-term lithium treatment.

In addition to hypermagnesaemia (P < 0.001), this group of patients had raised plasma levels of aldosterone (P < 0.001) and increased plasma renin concentration (P < 0.05). Serum magnesium was positively correlated to plasma aldosterone (r = 0.58, P < 0.02).

The relation between activation of the renin-aldosterone system and the presence of hypermagnesaemia during chronic lithium treatment could conceivably be mediated through a lithium-induced hypovolaemic state.
RADIOIMMUNOASSAY FOR PORCINE PROLACTIN: PLASMA LEVELS DURING LACTATION, SUCKLING AND WEANING AND AFTER TRH ADMINISTRATION
Authors: van Landeghem A. A. J. , van de Wiel D. F. M.
Published: December 2008

A sensitive heterologous radioimmunoassay for porcine prolactin (pPRL) has been developed. Anti-ovine prolactin antibody was raised in rabbits which allowed a final dilution of 1:500 000. The separation of free and antibody bound [125I]pPRL is based on the double antibody solid phase system. The assay is specific for pPRL. There is no cross-reaction with pLH, pFSH and pTSH; little cross-reaction (1.35 %) was found with pGH. The smallest detectable amount was 0.08 ng per tube. During lactation high plasma levels are found with great fluctuations. After weaning the plasma PRL levels fall to basal levels within a few hours. After thyrotrophin-releasing hormone (TRH) administration plasma concentrations increase within a few minutes.
THE RELATIONSHIP BETWEEN LEVELS OF THYROID STIMULATING HORMONE AND OF THYROXINE AND TRIIODOTHYRONINE IN BLOOD OF HYPOTHYROID PATIENTS
Authors: Johansen Klaus , Hansen Jens Mølholm , Skovsted Lis
Published: December 2008

Serum TSH values and the free concentration of T4 and T3 in serum expressed as the free T4- and T3-indices showed a curvilinear relationship in 24 patients with manifest hypothyroidism mainly due to extremely elevated serum TSH levels associated with very low thyroid hormone levels.

The same degree of negative correlation was found between the log serum TSH concentration and serum free T4-index (r = −0.51, P < 0.05) and between log serum TSH concentration and serum free T3-index (r = −0.47, P < 0.05). The correlation coefficients dropped to non-significant levels when the interdependence between the free T3- and T4-indices was taken into account and eliminated by partial correlation analysis.

The degree of negative correlation between serum TSH and the thyroid hormones was also of the same order of magnitude in 5 hypothyroid patients studied prospectively during treatment with L-thyroxine (TSH vs. T4: mean r = −0.71; TSH vs T3: mean r = −0.79).
A CASE OF HASHIMOTO'S THYROIDITIS WITH THYROID IMMUNOLOGICAL ABNORMALITY MANIFESTED AFTER HABITUAL INGESTION OF SEAWEED
Authors: Okamura Ken , Inoue Kenjiro , Omae Teruo
Published: December 2008

An interesting case of iodide induced goitre with immunological abnormalities is described. The patient who was sensitive to synthetic penicillin had previously been treated for exudative pleuritis, congestive heart failure and acute renal failure. Following recovery, he began to ingest large amounts of seaweed after which he developed goitrous hypothyroidism. It was of interest that the serum level of gamma-globulin increased, and subsequently the antithyroid microsomal antibody became strongly positive, suggesting that thyroidal autoimmune processes had been precipitated. Biopsy of the thyroid gland revealed chronic thyroiditis, with evidence suggesting extreme stimulation by TSH. High thyroidal uptake of 131I, positive perchlorate discharge test and biochemical analysis of the thyroidal soluble protein showed severe impairment of hormone synthesis following continuous accumulation of excess iodide. While there is evidence suggesting that increased iodide may be an important factor in the initiation of Hashimoto's thyroiditis, this may result from the marked increased sensitivity of Hashimoto's gland to the effects of iodine. Thus an occult lesion could be unmasked in this manner. The mechanism by which iodide mediates this effect is not clear.
SEX DIFFERENCES IN CATECHOLAMINE CONTENT IN DISCRETE BRAIN NUCLEI OF THE RAT: EFFECTS OF NEONATAL CASTRATION OR TESTOSTERONE TREATMENT
Authors: Crowley W. R. , O'Donohue T. L. , Jacobowitz D. M.
Published: December 2008

Dopamine and norepinephrine levels were measured in individual brain nuclei in normal adult male and female rats and in adult male rats castrated on day 1 of life and in adult female rats given 1.25 mg testosterone propionate on day 4 of life. Normal adult males showed higher concentrations of dopamine than females in the caudate, tractus diagonalis and arcuate nuclei and in the median eminence. Day 1 castration of males reduced the dopamine levels of the arcuate nucleus and nucleus of the tractus diagonalis, while neonatal administration of testosterone to females elevated the dopamine concentration of the arcuate nucleus and nucleus of the tractus diagonalis. Normal adult males had higher concentrations of norepinephrine than females in the preoptic-suprachiasmatic, paraventricular, periventricular, and arcuate nuclei and in the median eminence. Neonatal endocrine manipulations (neonatal male castration and female testosterone treatment) failed to alter significantly these sex differences. The results suggest a sexual dimorphism in the catecholamine innervation of certain discrete areas of the brain and that the dopamine concentration in the arcuate and tractus diagonalis nuclei is influenced by perinatal androgen.
EFFECTS OF TWO SUBSTITUTED BENZAMIDES, TIAPRIDE AND SULTOPRIDE, ON GONADOTROPHINS AND PROLACTIN
Authors: L'Hermite M. , MacLeod R. M. , Robyn C.
Published: December 2008

The acute effects in the human of tiapride and sultopride, two new substituted benzamides related to sulpiride, were studied with respect to gonadotrophins (LH and FSH) and prolactin (PRL) secretion. Two different groups of 3 normal men and 3 normally cycling women received im injections of either 100 mg sultopride or 200 mg tiapride. Five min after the injection of either psychotropic drug, the serum PRL concentration increased significantly (P < 0.001 by variance analysis) and reached maximal values by 30 min and remained elevated for at least 6 h; women tended to release more prolactin than men.

Although tiapride (500 nm) had no direct effect on the in vitro synthesis or secretion of prolactin, the drug blocked the inhibitory action of dopamine (500 nm) on the secretion of prolactin. Rats bearing a transplantable prolactin-secreting pituitary tumour MtTW15 have extremely high serum prolactin and through an autofeed mechanism the host's pituitary gland is suppressed. The in vitro synthesis and secretion of prolactin by these rats' pituitary gland is decreased. The in vivo administration of tiapride to these tumour-bearing rats restored the in vitro secretion of prolactin to control values. The in vitro data support the concept that tiapride increases prolactin secretion directly at the pituitary level by blocking the inhibitory activity of dopamine; an additional effect at a higher level can not, however, be ruled out.

In vivo in the human, no significant modification of LH and FSH occurred after either drug, suggesting that the menstrual cycle disturbances observed during chronic treatment with tiapride might be related to hyperprolactinaemia or be the result of a mechanism similar to that inducing hyperprolactinaemia.
CALCITONIN HETEROGENEITY IN LUNG CANCER AND MEDULLARY THYROID CANCER
Authors: Becker Kenneth L. , Snider Richard H. , Silva Omega L. , Moore Charles F.
Published: December 2008

An investigation was made of the increased serum calcitonin in patients with medullary thyroid cancer and bronchogenic carcinoma in order to determine whether these conditions can be differentiated immunochemically. Endogenous fractions of immunoreactive calcitonin were separated by gel filtration and radioimmunoassayed with calcitonin antibodies having different region specificities. The pattern of serum heterogeneity of patients with medullary thyroid cancer was characterized by the presence of at least seven different fractions of immunoreactive calcitonin, ranging from fraction I (≧ 30 000 molecular weight (MW)) to fraction V (~ 2500 MW). In contrast, most patients with bronchogenic cancer had a predominance of high MW fractions (i. e. fractions I and II A). Following in vitro incubation of the serum, the typical large MW pattern of bronchogenic cancer serum could be converted to the more diffuse pattern seen in the serum of medullary thyroid cancer. We were able to differentiate, pre-operatively, the hypercalcitonaemia serum of medullary thyroid cancer patients from that of bronchogenic cancer patients by determination of the ratio of calcitonin as radioimmunoassayed with midportion versus carboxyl terminal antibody.
BINDING OF GONADOTROPHIN RELEASING HORMONE (GnRH) BY BOVINE ANTERIOR PITUITARY PLASMA MEMBRANES AND PURIFIED GnRH RECEPTOR PROTEIN (GnRH.R)
Authors: Zolman Joseph C. , Valenta Lubomir J.
Published: December 2008

[125I]-(GnRH) concentration dependence binding curves using isolated bovine anterior pituitary plasma membranes, intact and solubilized, and purified GnRH receptor protein, are compared. In all instances the concentration dependence binding curves had a stepwise character here interpreted as multisigmoid, with several steep increases and plateaus. These curves are compatible with the existence of several binding sites for GnRH. Purification of the GnRH receptor protein (GnRH.R) resulted in about 500 000-fold increase of binding activity and yielded a single protein species on polyacrylamide gel electrophoresis in SDS, of estimated molecular weight 60 000. Similarity of GnRH binding by the purified protein with that of intact and solubilized plasma membranes suggested that a single protein was responsible for the binding in each instance. Thus heterogeneity of GnRH binding is likely attributable to phase transitions of a single receptor protein into different allosteric forms. The data suggest that positive cooperativity is involved in the studied system.
TIME-DEPENDENT DECREASE OF PITUITARY RESPONSE TO LH-RH AFTER CHRONIC TREATMENT OF INTACT FEMALE RATS WITH ETHINYLOESTRADIOL AND NORETHINDRONE
Authors: Kuhl Herbert , Sachs Angelika , Rosniatowski Christian , Taubert Hans-Dieter
Published: December 2008

The effect of daily injections of 50 μg ethinyloestradiol and 1 mg norethindrone upon basal and LH-RH-stimulated LH release was investigated in intact adult female rats during a period of 30 days. Basal plasma LH was depressed by about 30 % during the whole time of steroid treatment, and returned to the level of the control values two weeks after discontinuation. The injection of 30 ng and 150 ng LH-RH into untreated rats resulted in a significant increase of plasma LH which was, however, not dose-dependent. After the treatment with ethinyloestradiol and norethindrone for 5 days, the pituitary response to 150 ng was approximately four times higher than that to 30 ng. The LH release after injection of 150 ng LH-RH decreased significantly with the duration of steroid treatment, and was totally abolished by 30 days; whereas two weeks after the termination of steroid application the pituitary responded to LH-RH in the same manner as in control rats. When 30 ng LH-RH were injected into oestrogen/norethindrone treated rats, no decrease in LH release was found until day 20 of the experiment. By 30 days of treatment no rise in plasma LH could be elicited.

The activity of the LH-RH-degrading enzyme L-cystine arylamidase was stimulated during the treatment with ethinyloestradiol and norethindrone in the pituitary by approximately 100 %, whereas almost no effect on this enzyme was seen in the hypothalamus.

It is concluded that the chronic treatment of intact female rats with ethinyloestradiol and norethindrone causes time-dependent and reversible alterations in the storage of LH in the pituitary. The elevated activity of the LH-RH-degrading enzyme in the pituitary is possibly involved in these processes and/or in the mechanism responsible for the depression of basal LH.
URINARY EXCRETION OF THYROXINE, TRIIODOTHYRONINE, 3,3′,5′-TRIIODOTHYRONINE (REVERSE T3) AND RENAL FUNCTION IN HUMAN NEWBORNS
Authors: Rogowski Preben , Faber Jens , Kirkegaard Carsten , Lundsteen Merete , Poulsen Dorte Loldrup , Siersbæ-Nielsen Kaj
Published: December 2008

The urinary excretion and serum levels of thyroxine (T4), triiodothyronine (T3) and 3,3′,5′-triiodothyronine (reverse T3) was estimated in a longitudinal study of human newborns. The maternal and cord blood was also studied. Neonatal renal function was evaluated using endogenous creatinine clearance. In cord blood serum T3 was found to be lower than in maternal blood, but reverse T3 highly elevated. During the first 5 days of life serum T4 and T3 increased with maximum at 48 and 24 h in contrast to reverse T3 which remained high and then declined rapidly after 4 days.

Creatinine clearance during the first 3 days of life increased from 5.3 to 21.9 ml/min/1.73 m2. In the same period the urinary T4 excretion increased from 79 to 281 ng/24 h, urinary T3 excretion from 16 to 44 ng/24 h and urinary reverse T3 from 4 to 15 ng/24 h. The renal excretion of thyroid hormones, corrected for body surface, was decreased compared to adult controls, corresponding to an immature renal function. The lack of ability to excrete thyroid hormones involved primary T3 and reverse T3 suggesting particular immaturity of tubular secretion of these hormones during the neonatal period.
EFFECTS OF SUBSTITUTION WITH THYROXINE ON THE THYROTROPHIN (TSH) RESPONSE TO THYROTROPHIN-RELEASING HORMONE (TRH) IN SEVERE PRIMARY MYXOEDEMA AND IN MILD HYPOTHYROIDISM FOLLOWING PROLONGED THYROSTATIC THERAPY
Authors: Fischer H. R. A. , Hackeng W. H. L. , Schopman W. , Silberbusch J.
Published: December 2008

The evolution of the thyrotrophin (TSH) response after 400 μg thyrotrophin-releasing hormone (TRH) was investigated during recovery of hypothyroidism.

In 14 myxoedematous patients, replacement therapy with thyroxine (T4) caused characteristic changes. Before treatment a relatively blunted pattern with mΔTSH1) of 51.2 ± 30.6 mU/1 was found. Two and 4 weeks after treatment an enhanced response was evolved with values for mΔTSH of 87.7 ± 43.4 and 96.0 ± 48.0 mU/1 (P < 0.02 respectively < 0.01). Comparison of the TSH curve showed significant increases in ΔTSH during the first 4 weeks of treatment at 20, 40 and 60 min compared to corresponding measurements in the basal state.

In 17 overtreated hyperthyroid patients with mild, mostly chemical hypothyroidism the influence of T4 replacement on TSH responses at different TSH levels was studied. At the stage of mild TSH elevation (3–10 mU/1) mΔTSH before and during substitution were 12.6 ± 6.7 and 25.9 ± 15.3 mU/1, respectively (P < 0.01). Moderate TSH elevation (10–25 mU/1) was accompanied by mΔTSH of 25.4 ± 13.4, respectively 44.5 ± 22.9 mU/1 (P < 0.01) while high TSH values (> 26 mU/1) had responses of 39.1 ± 16.0 and 92.5 ± 22.0 mU/1 (P < 0.001). In these patients the initial blunting of TSH responses could not be attributed to the foregoing toxicosis, since follow up during 6–15 weeks of protracted hypothyroidism did not show any tendency to enhancement of relative release (% mΔTSH).

These findings suggest that in the early stage of replacement therapy of hypothyroidism, either pituitary TSH is accumulating or that endogenous TRH is declining.
REGULATION OF PANCREATIC GLUCAGON SECRETION DURING A CONTINUOUS GLUCOSE INFUSION IN EARLY AND OVERT DIABETICS
Authors: Schulz B. , Ziegler M. , Witt S. , Rjasanowski I. , Heinke P. , Bibergeil H.
Published: December 2008

The pancreatic glucagon (IRG) secretion pattern was studied during a 2 h glucose infusion test (12 mg/kg/min) in 21 controls as well as in 44 subjects showing different degrees of carbohydrate intolerance.

The fasting IRG levels increased significantly from controls (98 ± 7.6 pg/ml) to chemical (144 ± 9 pg/ml) and mild maturity-onset-type diabetics (166 ± 12.2 pg/ml).

During artificial hyperglycaemia the glucagon concentrations decreased slightly in all groups, but they remained at a higher level in early and overt diabetics1). The molar IRI-IRG ratios have been found to be diminished in patients displaying a disturbed carbohydrate tolerance. There was not any correlation between insulin and glucagon concentrations in the blood.

The findings suggest that abnormalities of alpha cell function may be present in early and overt diabetes independent of beta cell responsiveness. The causal relationship of A and B cell function in glucose intolerant subjects has to be cleared in follow-up studies.
IN VITRO AND IN VIVO STUDIES ON LEYDIG CELL FUNCTION IN OLD RATS
Authors: Pirke Karl M. , Vogt Hermann-J. , Geiss Michael
Published: December 2008

Young adult (3 months old) and old (26–28 months old) male Wistar rats were studied. Testicular weight was 1.66 g (range: 1.33 – 2.86) in the younger group and 1.62 g (range: 1.04 – 1.90) in the older group. The total Leydig cell volume as measured by a quantitative histometric method was significantly larger in the old animals (x̄ = 0.153 ml vs. x̄ = 0.089 ml). The testicular HCG binding capacity was 2.54 ng HCG per 100 mg tissue (range: 1.88 – 3.77) in the younger animals and 1.83 ng HCG per 100 mg tissue (range: 0.80 – 3.02) in the older ones (P < 0.01). Plasma testosterone was on an average 242 ng/100 ml (range: 72 – 1162) in the young adult rats and 91 ng/100 ml (range: 23 – 277) in the older rats. Plasma LH was only slightly (P < 0.05) decreased and was 49 ng LH–RP–1/ml (range: 14 – 120) in the younger group and 40 ng LH–RP–1 ng/ml (range: 5 – 98) in the older.

When the testicular tissue pieces were incubated with different doses of HCG or dibutyryl cAMP and testosterone production was measured, identical dose-response curves for old and young tissue were obtained. After in vitro incubation with a NADPH generating system, which under the conditions used was a much stronger stimulus for steroid biosynthesis than HCG or dibutyryl cAMP, the tissue of young rats produced about twice the amount of testosterone and testosterone precursors (pregnenolone, progesterone, 17α-hydroxyprogesterone and androstenedione) than old tissue.
EFFECTS OF MEDIAL HYPOTHALAMIC DEAFFERENTATION ON PROLACTIN SECRETION IN PSEUDOPREGNANT RATS
Authors: Kato H. , Velasco M. E. , Rothchild I.
Published: December 2008

Frontal hypothalamic deafferentation (FHD), which disconnects the anterior hypothalamus from the preoptic area, stops the twice daily surges of prolactin secretion of pregnancy or pseudopregnancy in the rat, and causes rapid luteolysis. Medial hypothalamic deafferentation (MHD), which separates the anterior from the posterior half of the hypothalamus, does not interrupt pregnancy and causes a significant increase in the size of the corpora lutea. To see whether MHD induces an increase in the basal level of prolactin secretion and/or a change in the pattern of prolactin surges, pseudopregnant rats were subjected to MHD or a sham operation on day 3 (day 1 = day of oestrus) and their bloods assayed for prolactin on either day 5 or days 7–8.

MHD caused a specific disappearance of the day-time prolactin surge and a diminution in the height of the night-time surge, but no change from the controls in the basal prolactin level. In spite of what thus appears to be a lesser secretion of prolactin than in the controls, the corpora lutea of the MHD rats were larger, and progesterone was secreted at a higher rate and for a longer time, than in the controls. The relation of these findings to the existence of a "surge centre" in the hypothalamus was discussed.
INFLUENCE OF THE PURITY OF THE IODINATED TRACER ON THE SPECIFICITY OF THE RADIOIMMUNOASSAY OF HUMAN LUTEINIZING HORMONE
Authors: Suginami H. , Robertson D. M. , Diczfalusy E.
Published: December 2008

Human luteinizing hormone (HLH) iodinated with 125I by the use of a lactoperoxidase method, was fractionated by either cellulose adsorption, gel filtration or by the combination of these methods. The products of iodination were characterized by their in vitro biological LH activity and by their binding profiles with antisera to HLH, HLHα and HLHβ subunits. Several radioactive components were obtained after gel filtration with or without an initial cellulose adsorption step. One of these fractions was identified as biologically active HLH and another as the HLHα subunit.

Radioimmunoassay studies were conducted with different iodinated fractions as tracers, using three well defined and widely available antisera to HLH. The standard used was the HLH International Reference Preparation for immunoassay (68/40). Cross-reactivity was examined with several purified pituitary preparations, such as HFSH, HTSH, HLHα and HLHβ subunit. A significantly higher cross-reactivity with HLHα, HFSH and HTSH was obtained with the [125I]HLHα fraction as tracer than with biologically active [125I]HLH. Furthermore, in the radioimmunoassay of HLH preparations of varying purity, significantly higher estimates of immunological activity were obtained with the [125I]HLHα tracer than with the biologically active [125I]HLH.

It is concluded that the presence of [125I]HLHα in the [125I]HLH tracer can result in serious overestimates of the immunological activity in the measurement of LH. Therefore [125I]HLHα should be separated from [125I]HLH prior to radioimmunoassay. Many of the fractionation methods commonly used (cellulose adsorption and short column gel filtration systems) are inadequate for this purpose. However, an adequate separation can be achieved by the use of high resolution gel filtration systems.
ADRENAL INVOLVEMENT IN THE TIMING OF PUBERTY IN FEMALE RATS: INTERACTION WITH SERUM PROLACTIN LEVELS
Authors: Gelato Marie C. , Meites J. , Wuttke W.
Published: December 2008

Female Sprague-Dawley derived rats were either sham-operated or adrenalectomized at 20 days of age. Treatment of separate groups of rats with progesterone, corticosterone or prolactin was started at 21 days of age, and was continued until the day of vaginal opening. Similarly treated rats were decapitated at 25, 29 and 33 days of age and at the day of vaginal opening and the sera were collected from each animal and assayed for prolactin, LH and FSH. All rats were decapitated between 4–6 p. m. Adrenalectomy, as previously reported, significantly delayed the day of vaginal opening. Prolactin treatment advanced the day of vaginal opening in intact rats and it restored the day of vaginal opening in adrenalectomized rats to that of intact control rats. Progesterone treatment always delayed the day of vaginal opening in intact rats. It caused an even greater delay in vaginal opening than adrenalectomy alone. Corticosterone treatment, on the other hand, was able to reverse the effect of adrenalectomy but had no effect on vaginal opening in intact rats. In intact rats serum prolactin levels rose steadily until the day of vaginal opening. Adrenalectomized and intact rats treated with progesterone had significantly decreased serum prolactin levels. However, in adrenalectomized corticosterone treated rats serum prolactin levels were significantly increased at all ages measured when compared to the untreated rats. The FSH and LH levels showed no significant changes during any of these experimental procedures. Approximately 50 % of the rats showed LH peaks on the day of vaginal opening as well as an increase in FSH. The data indicate a prolactin-adrenal interaction for the timing of the onset of puberty in immature rats, assuming that the day of vaginal opening in association with increased gonadotrophin levels is an indicator for the occurrence of puberty.
INFLUENCE OF THIAZIDES ON THYROID PARAMETERS IN MAN
Authors: Bech Karine , Skovsted Lis , Siersbæk-Nielsen Kaj , Hansen Jens Mølholm
Published: December 2008

Iodine metabolism and thyroid hormones in blood were studied in 19 men and 11 women who had been treated with thiazides for arterial hypertension from 1 month to 15 years. The results were compared with the findings from age-matched normal controls. No differences were found regarding 24-h 131I-thyroid uptake, thyroid iodide clearance, renal iodide clearance, plasma inorganic iodide, absolute iodine uptake (AIU), serum thyroxine (T4 (D)), resin T3 test (T3U) and TSH after TRH. Twenty-four-hour urinary iodine was higher in the patients treated with diuretics which could be explained by increased iodine intake. The findings of increased serum triiodothyronine (T3 (RIA)) and reverse T3 (rT3) might be due to changes in distribution volume in the thiazide-treated patients. Long-term treatment with thiazides in man do not lead to iodine depletion.
RELEASE OF CYCLIC AMP FROM THYROID CELLS IN VITRO
Authors: Ahrén Bo , Gustafson Åsa , Hedner Pavo , Nilsson Hans
Published: December 2008

Half lobes of mouse thyroid gland were incubated in vitro with TSH. They released cyclic AMP (cAMP) into the medium in amounts depending on the concentration of TSH. The release of cAMP was greatest during the first hour of incubation, then it occurred at a lower rate. With an incubation time of 45 min the medium cAMP levels ranged from 43.0 ± 11.9 pmole per mg tissue protein for controls to 296.5 ± 29.2 pmole per mg tissue protein with 5 mU of TSH in the medium.

The tissue cAMP level reached a maximum after 15–30 min of incubation with TSH, then it gradually decreased towards control level during 4 h of incubation. With 25 min of incubation the tissue cAMP level was 28.5 ± 8.8 pmole per mg tissue protein for controls compared to 194.3 ± 27.0 pmole per mg tissue protein with 5 mU TSH in the incubation medium.

The release of thyroxine was of the same order during the later part of the 4 h incubation period compared to the first one.

The results illustrate the quantitative importance of cAMP release, and the fact that in the later part of the incubaion period the cell content of cAMP was low while the release of thyroxine remained high.
DEVELOPMENTAL PATTERNS OF PLASMA AND TESTICULAR TESTOSTERONE IN MICE FROM BIRTH TO ADULTHOOD
Authors: Jean-Faucher Ch. , Berger M. , de Turckheim M. , Veyssiere G. , Jean Cl.
Published: December 2008

Male mice were raised in cohabitation with females from birth to 90 days. Testosterone was measured every 10 days in plasma and testes. Sex difference in body weight was related to the pre-pubertal increase of testosterone levels in males. The weight of the seminal vesicle was positively correlated with circulating testosterone levels between 1 and 40 days but not between 50 and 90 days

Testosterone concentrations in the plasma and testes were high at birth: 630 pg/ml and 58.0 ± 17.7 ng/100 mg; they subsequently decreased during the first days of life and remained low until day 20: 240 ± 110 pg/ml and 0.1 ± 0.03 ng/100 mg. The testosterone levels then increased rapidly between days 20 and 30 and especially between 30 and 40 reaching their maxima: 5770 ± 1720 pg/ml and 123.7 ± 18.3 ng/100 mg testis. This increase was transitory and testosterone levels fell after day 40. By 90 days, the testosterone levels, 440 ± 65 pg/ml and 43.2 ± 5.5 ng/100 mg testis, were comparable to those measured at birth. Plasma testosterone and age were positively correlated between 1 and 40 days, and negatively between 50 and 90 days.

The first fertile matings occurred at age 40 days.
HYPERPROLACTINAEMIA IN THE SPONTANEOUSLY HYPERTENSIVE RAT
Authors: Sowers James R. , Resch Garth , Tempel George , Herzog Jacques , Colantino Marta
Published: December 2008

A hypothalamic role in the aetiology of hypertension in the spontaneously hypertensive rat (SHR) has been suggested by prior observations. In an attempt to determine whether the central control of prolactin (PRL) release is altered in the SHR we have compared the PRL response to immobilization stress, thyrotrophin releasing hormone (TRH), haloperidol, and l-DOPA in the SHR and in normotensive Wistar control rats. Carotid artery catheters were inserted 48 h prior to the PRL response studies and the catheters were maintained patent with heparinized saline. Timed blood samples were obtained in SHR and control rats weighing 180-225 g. The SHR demonstrated elevated basal serum levels of PRL and greater PRL responses to stress. However, administration of l-DOPA resulted in a similar suppression of serum PRL in the SHR and in the normotensive controls. These findings suggest alteration in the central control of PRL release in the SHR. Observations of elevated basal PRL, exaggerated PRL in response to l-DOPA in SHR are consistent with normal pituitary responsiveness to dopamine suppression of PRL release, but defective hypothalamic metabolism of dopamine. Alterations in central dopamine control mechanisms in the SHR may play a role in the pathogenesis of essential hypertension in these animals.
SERUM THYROTROPHIN AND CIRCULATING THYROGLOBULIN AND THYROID MICROSOMAL ANTIBODIES IN A FINNISH POPULATION
Authors: Gordin A. , Maatela J. , Miettinen A. , Helenius Tuula , Lamberg B.-A.
Published: December 2008

Circulating thyroglobulin antibodies (TgA) were detected in 7.9 % and thyroid microsomal antibodies (MsA) in 25.8 % of a sample of 507 subjects in the adult population of southern Finland when titres as low as 1/5 for TgA and 1/10 for MsA were included. Both antibodies were measured by passive haemagglutination techniques. The prevalence of high titres was 0.6 % for TgA (≥ 1/25 000) and 4.2% for MsA (≥ 1/100 000). Eightyeight per cent of the TgA positive subjects also had MsA. The MsA titres were usually markedly higher than those of TgA in the same subjects.

Serum thyrotrophin (TSH), cholesterol and triglycerides were measured in 123 euthyroid subjects with thyroid antibodies and no history of thyroid diseases, and in controls matched for age and sex. Serum TSH was elevated in 31 % of the TgA positive subjects and the mean TSH concentration was significantly above that of the controls. All 3 subjects with high TgA titres also had elevated TSH levels. Serum TSH concentration was increased also in 25 % of those with MsA and the mean TSH value was significantly above the control level. High MsA titres were found in 19 subjects and the serum TSH was elevated in 10 of them (53%). The prevalence of symptomless autoimmune thyroiditis (SAT) was 2 and 5 %, of the population when high titres of either TgA or MsA, respectively, and elevation of serum TSH was used as criteria. This fits with our previous observations. There was no difference in serum cholesterol or triglycerides in the TgA or MsA positive subjects or in the corresponding matched controls.
PLASMA CYCLIC NUCLEOTIDE LEVELS IN HYPERTHYROIDISM
Authors: Lin Tu
Published: December 2008

Plasma cyclic AMP and cyclic GMP levels were studied in a group of normal subjects and 10 subjects with hyperthyroidism. In the control group, mean plasma cyclic AMP levels were 15.3 ± 1.3 nmol/l (sem), and plasma cyclic GMP levels were 9.4 ± 0.58 nmol/l (sem). In untreated hyperthyroid subjects, both plasma cyclic AMP and cyclic GMP levels were significantly elevated above normal with mean values of 35.0 ± 2.4 nmol/l (sem) (P < 0.001) and 14.7 ± 0.2 nmol/l (sem), (P < 0.001), respectively. Six of the hyperthyroid subjects were re-studied when they became euthyroid; plasma cyclic nucleotide concentrations all fell within the normal range. To evaluate the relative contribution of triiodothyronine and thyroxine to elevated plasma cyclic nucleotide levels, two hyperthyroid subjects were treated with propylthiouracil and iodide. Plasma cyclic nucleotide levels were normalized when plasma triiodothyronine levels declined to normal range, at the time when plasma thyroxine levels were still elevated. These preliminary data suggest that increased triiodothyronine production is responsible for the increased cyclic nucleotide levels in hyperthyroidism.
NORMALIZATION OF THE INSULIN SENSITIVITY AND THE CELLULAR INSULIN BINDING DURING TREATMENT OF OBESE DIABETICS FOR ONE YEAR
Authors: Beck-Nielsen Henning , Pedersen Oluf , Lindskov Hans Otto
Published: December 2008

The relative importance of the insulin resistance, the decreased cellular insulin binding and the relative insulin deficiency in the pathogenesis of diabetes mellitus in obese subjects has been studied.

Ten obese diabetics were studied before and during treatment for 1 year with a 1200-1500 kcal's diet.

No change was found in the insulin response to iv injection of glucose during treatment (P > 0.1), whereas the insulin sensitivity was normalized after 1 year (P < 0.01). In parallel to the clinical normalization and the improvement of the insulin sensitivity the insulin binding to monocytes was normalized (P < 0.01).

We conclude that both the insulin resistance and the relative insulin deficiency are of decisive importance in the pathogenesis of diabetes mellitus of the obese. The insulin receptor defect seems to be one of the major factors responsible for the insulin resistance.