bluuebunny/crossref_metadata_2025 huggingface dataset:
COMPARISON OF TWO TESTS FOR HETEROZYGOSITY IN CONGENITAL ADRENAL HYPERPLASIA (CAH)
Authors: Weil J. , Bidlingmaier F. , Sippell W. G. , Butenandt O. , Knorr D.
Published: December 2008

The increase of plasma cortisol (F), androstenedione (A), 17α-hydroxyprogesterone (17-OH-P) and testosterone (T) was measured after iv administration of ACTH in heterozygotes for CAH and in controls under two different conditions:

Test 1: ACTH stimulation was performed without any particular preparation.

Test 2: 1.5 mg of dexamethasone (dex.) was given the evening before the ACTH stimulation.

Plasma F, A, 17-OH-P and T were measured by specific radioimmunoassays (RIA). Following ACTH stimulation, the increase of 17-OH-P was significantly higher in CAH-heterozygotes than in controls in both tests (P < 0.0005). Heterozygotes were characterized by a 17-OH-P increase after ACTH stimulation exceeding the +2 sd limit of the 17-OH-P increase found in controls. The detection of female heterozygotes was considerably improved by the administration of dex. before testing (test 2). In males, however, a better identification of heterozygotes was obtained without previous administration of dex. (test 1). By these tests, 100% of female (test 2) and 79% of male (test 1) CAH heterozygotes could be correctly identified.

There were no significant differences in the levels of F, A and T between heterozygotes and controls except for decreased T levels in test 1 (2P < 0.01) in most male heterozygotes after ACTH stimulation.
THE HISTOGENESIS OF THE ADRENAL CORTEX IN THE FOETAL SHEEP
Authors: Robinson Peter M. , Rowe Elisabeth J. , Wintour E. Marelyn
Published: December 2008

The cortex of sheep foetal adrenal glands from 25 days gestation until newborn (term equals 147 ± 3 days) were examined by light and electron microscopy. Three stages of development are of particular importance in relating structure to function: 1) from 35 to 60 days, 2) from 60 to 120 days and 3) from 120 days to term.

Between 35 and 60 days one cortical cell type predominated. It contained mitochondria with lamellar and vesicular cristae, scattered long strands of granular endoplasmic reticulum and only small amounts of smooth endoplasmic reticulum. After about 60 days two zones were apparent in the cortex and chromaffin cells became concentrated in the medulla. After 80 days the outer zone contained cells which resembled mature zona glomerulosa cells and the cells in the inner zone remained like those seen between 35 and 60 days, except they contained even less smooth endoplasmic reticulum. However, after about 90 days a small number of deep inner zone cells contained mitochondria with vesicular cristae which thus resemble mitochondria in the mature zona fasciculata. From about 120 days there was an increase in the number of cells in the inner zone that contained mitochondria with vesicular cristae. These cells also contained substantial quantities of smooth endoplasmic reticulum. At term most inner zone cells have this mature appearance.

Thus there is no "foetal cortex" in the sheep analogous to that found in human adrenal development, i. e. there is no prominent zone of cells containing large amounts of smooth endoplasmic reticulum which is present throughout most of the foetal period of development, and which regresses at birth. The structure of the cells present between 35 and 60 days was unexpected because it has been shown previously that sheep foetal adrenals of this age are capable of producing relatively large quantities of steroid hormones. However, the appearance of cells resembling mature zona glomerulosa cells at about 80 days correlates with the previously demonstrated ability of sheep adrenal glands of this age to produce relatively large quantities of aldosterone. The rapid development of numbers of mature cells in the last 3 weeks of gestation correlates with the previously described ability of near term sheep foetal adrenals to produce very large quantities of steroid hormones.
THE EFFECT OF SHORT-TERM TESTOSTERONE TREATMENT IN BOYS WITH DELAYED PUBERTY
Authors: de Lange W. E. , Snoep M. C. , Doorenbos H.
Published: December 2008

Eight boys with severely delayed puberty without pathological cause were treated for 6 months with testosterone. This resulted in acceleration of skeletal maturation and a marked increase in height and weight. No adverse effects were found on hypothalamic-pituitary and gonadal maturation. Basal LH, FSH and testosterone levels rose to nearly adult values at follow-up within a year and pituitary responsiveness to LH-RH increased markedly.
EFFECT OF ANDROGEN ON GROWTH HORMONE SECRETION AND GROWTH IN BOYS WITH SHORT STATURE
Authors: Martin Luis G. , Grossman Milton S. , Connor Thomas B. , Levitsky Lynn L. , Clark John W. , Camitta Francine D.
Published: December 2008

The response of plasma growth hormone (GH) to insulin-induced hypoglycaemia (IIH) and arginine infusion (AI) was studied in 22 young males (ages 8 to 17 years) with short stature and absent or delayed sexual maturation, before and after androgen administration. During initial evaluation, 5 patients had blunted GH response to IIH, 12 responded subnormally to AI and 4 failed to respond normally to either stimulus. These same studies were repeated in each patient following androgen administration. The source of androgen was as follows: a) 5 days of testosterone propionate (25 mg intramuscularly daily) in 20 patients. b) Methyltestosterone, 10 mg t. i. d. orally for four days in the other 2 subjects. In almost every case, androgen administration resulted in raising the levels of fasting GH and enhancement of the GH responses to IIH and AI was observed. Patients manifesting subnormal GH responses to these stimuli before androgen consistently demonstrated a normal response when challenged with identical stimuli during androgen administration. Growth velocities during the year following these studies were significantly increased in most instances and the growth spurts correlated well with the progression of sexual maturation. Sustained improvement in the GH responses to IIH and AI were uniformly observed in 3 patients when repetitive studies were performed 8 to 12 months later during spontaneous advancing sexual development. The results indicate that brief androgen administration can be helpful in delineating the cause of growth retardation in boys with short stature and delayed sexual maturation, particularly when the diagnosis of isolated growth hormone deficiency is suspected. They also offer prognostic value in determining growth potential in this same group of young males.
INHIBITION OF PROLACTIN AND LACTATION BY METHYLERGOMETRINE HYDROGENMALEATE
Authors: Peters F. , Lummerich M. , Breckwoldt M.
Published: December 2008

Reports on the effect of methylergometrine hydrogenmaleate1) (MEM) on prolactin (PRL) secretion and lactation are still controversial. Therefore a prospective study was designed to follow the influence of MEM on post-partum PRL levels and milk production. MEM was given orally to 30 post-partum women from day 1 to day 7 in a daily dose of 0.6 mg. Thirty untreated women served as control. PRL plasma levels and milk yield were compared at day 1, 3 and 7. PRL levels were significantly lower in the treated group at day 7 (P < 0.01), while the difference at day 3 was statistically not significant. Milk yield was significantly reduced at day 3 (P < 0.05) and day 7 (P < 0.01).

These results indicate PRL inhibiting properties of MEM resulting consequently in reduced lactation.
A SENSITIVE AND SPECIFIC IN VITRO BIOASSAY METHOD FOR THE MEASUREMENT OF FOLLICLE-STIMULATING HORMONE ACTIVITY
Authors: Van Damme M.-P. , Robertson D. M. , Marana R. , Ritzén E. M. , Diczfalusy E.
Published: December 2008

An in vitro bioassay method for hFSH is presented. The method is based on the principles previously described by Dorrington et al. (1976b) and involves the assay of oestradiol produced from 19-hydroxyandrostenedione by dispersed Sertoli cells of 10-day old rats when cultured in the presence of graded doses of FSH. Using the 1st International Reference Preparation for human pituitary gonadotrophins (FSH and LH/ICSH) for bioassay (code no. 69/104) as standard, the useful range of the method is from 0.5 to 32 mIU/chamber (2 to 128 mIU/ml). The sensitivity of the method is 0.5 mIU/chamber. The mean index of precision  obtained from 16 multiple assays over 2 or 3 dose levels was 0.084. Parallelism was obtained between the 69/104 preparation and all preparations under study. The practicability of the proposed assay method is such that 15 preparations at 3 dose levels can be assayed by one person in 3 days. The specificity of the assay was investigated by determining the FSH activity in the following preparations: hFSHa-α and β-subunits, hLH, hCG, hTSH, ACTH, human growth hormone (hGH) human prolactin (hPRL) and luteinizing hormone-releasing hormone (LH-RH). The ACTH, hGH, hPRL and LH-RH preparations studied showed no detectable FSH activity in the assay. In the remaining preparations very low levels of FSH activity were found, corresponding to 0.004 to 0.6 % of the weight of these preparations when compared with a highly purified hFSH preparation, suggesting that the method is specific for FSH. The possible synergistic or antagonistic influence of the above preparations when assayed in the presence of the 69/104 preparation was also assessed. No evidence of a synergistic or antogonistic effect was found. The assay of the hFSH potencies of a limited number of hFSH preparations of varying purity by the proposed in vitro bioassay, an hFSH radioreceptor method and an hFSH specific radioimmunoassay technique revealed that – although the relationship of the various potencies obtained with each method showed a close agreement – the bioassays yielded the highest potency estimates, and the radioimmunoassays the lowest ones.

Since the proposed bioassay method is sensitive and considered to be specific for hFSH activity, it provides a suitable basis for the assessment of the specificity of other in vitro methods (radioreceptor and radioimmunoassay) currently used for detecting low levels of FSH activity.
EFFECTS OF METHYLMERCAPTOIMIDAZOLE (MMI), PROPYLTHIOURACIL (PTU), POTASSIUM PERCHLORATE (KClO4) AND POTASSIUM IODIDE (KI) ON THE SERUM CONCENTRATIONS OF THYROTROPHIN (TSH) AND THYROID HORMONES IN THE RAT
Authors: Männistö P. T. , Ranta T. , Leppäluoto J.
Published: December 2008

Male Sprague-Dawley rats were given graded doses of methylmercaptoimidazole (MMI), propylthiouracil (PTU), KClO4 or KI in drinking water for 4 days, or the lowest effective dose of each drug for various times. The rats were sacrificed at 1–2 p. m. and serum T3, T4 and TSH concentrations were measured by radioimmunoassays. It was found that administration of 5 mg/l of MMI, 10 mg/l of PTU and 100 mg/l of KClO4 for 4–14 days induced a transient rise in serum TSH and a fall in serum T3 or T4 or in both. The effects of KI were not consistent. In another series of experiments, PTU (10 mg/l) was given in drinking water for 4 days, and then graded doses of T3 or T4 were given iv, or 100 ng of TRH was injected into a tail vein, or the animals were exposed to 4°C for 30 min. The initial high TSH levels were further increased by TRH and cold and decreased by T3 and T4. The PTU-treated animals had goitres after 4 days. We infer that low doses, that is to say 10–100 times lower than previously described, of antithyroid drugs induce a hypothyroidism characterized by an increased TSH level and a decreased serum T3 or T4 level or both. A 4 days' treatment with PTU (10 mg/l in tap water) is a suitable tool for studying the effect of various conditions on TSH secretion.
EFFECT OF TWO SULPHONYLUREAS ON THE DOSE KINETICS OF GLUCOSE – INDUCED INSULIN RELEASE IN NORMAL AND DIABETIC SUBJECTS
Authors: Cerasi Erol , Efendic Suad , Thornqvist Christina , Luft Rolf
Published: December 2008

The effect of two second generation sulphonylureas, gliquidone and glibenclamide, on insulin secretion has been studied in the basal state and in combination with glucose infusions in normal controls, patients with mild maturity-onset diabetes, and subjects with normal glucose tolerance but low insulin response. When injected intravenously, gliquidone caused rapid elevation of plasma insulin, peaking at 5 min in all groups, while glibenclamide induced a slow rise in insulin. Insulin response was somewhat smaller than normal in diabetics and low insulin responders. In all groups, 25 μg/kg glibenclamide and 200 μg/kg gliquidone were equipotent in generating an insulin response at the basal state.

Equipotent amounts of sulphonylureas were combined with glucose infusions at three different dose levels. The glucose-insulin dose relationships, established by giving glucose alone, demonstrated curves that were flatter, and shifted to the right of the control in diabetics and low insulin responders, the changes being more marked in the former group. Addition of sulphonylurea induced a left shift in the dose-response relationships in controls and low insulin responders; under these conditions the effect of glibenclamide was more pronounced than that of gliquidone. The doseresponse relation for glucose-induced insulin release was completely normalized in low responders when sulphonylureas were added. In the group of mild diabetics, insulin response to glucose was enhanced by sulphonylureas only to a modest extent, the dose-response curves remaining grossly abnormal.

It is concluded that, under acute experiments, sulphonylureas correct the deficient insulin response only in subjects with minimal abnormalities of the glucose tolerance; their effect in diabetics, even very mild ones, is marginal.
INHIBITION OF DIPHOSPHONATE-BLOCKED BONE MINERALIZATION. EVIDENCE THAT CALCITONIN PROMOTES MINERALIZATION
Authors: Boris Alfred , Hurley James F. , Trmal Thelma , Mallon John P. , Matuszewski Diana S.
Published: December 2008

There is much experimental evidence which indicates that calcitonin inhibits bone mineral resorption, but there are few data available in support of the proposal that calcitonin may also promote mineralization. Ethane-1-hydroxy-1,1-diphosphonate (EHDP) administered to immature rats inhibited mineralization as evidenced by widened tibial epiphyseal plates and decreased bone ash to dry weight ratios. Concurrent dosing with salmon calcitonin (SCT) prevented or reversed the EHDP-blocked mineralization in a dose dependent manner.

Administration of SCT during the period after EHDP treatment significantly improved mineralization of tibial epiphyseal plates as shown by plate width narrowing and increased uptake of radioactive calcium. These results suggest that SCT increased mineralization in EHDP-treated rats, and provide supportive evidence for the proposal that calcitonin may also promote mineralization, in addition to its well known ability to inhibit bone mineral resorption.
BIOCHEMICAL AND HISTOLOGICAL STUDIES ON PROSTATES IN CASTRATED DOGS AFTER TREATMENT WITH ANDROSTANEDIOL, OESTRADIOL AND CYPROTERONE ACETATE
Authors: Tunn U. , Senge Th. , Schenck B. , Neumann F.
Published: December 2008

The effect of cyproterone acetate (CA) on experimentally induced benign prostatic hyperplasia (BPH) in the castrated dog was investigated. BPH was induced by 6 months' treatment with 3α-androstanediol (3α-diol) alone and in combination with 17β-oestradiol (Oe2). RNA, DNA and zinc content of the glands were determined in addition to histological examination and measurement of the prostates. Two different types of prostatic enlargement were observed. First, 3α-diol induced typical diffuse canine hyperplasia with replacement of functional activity. DNA, RNA and the zinc content of total glands were increased compared with intact controls. Second, 3α-diol plus Oe2 produced on the one hand a more striking increase of prostatic weights, but on the other a loss of typical morphological structure and function. Histologically, transformation of simple glandular epithelium into stratified squamous metaplasia occurred in addition to stimulation of fibromuscular tissue. Biochemically, a relative decrease of DNA per mg tissue was measured with a fall in the RNA to DNA ratio and zinc to the values of castrates. Administration of CA resulted in an abolition of the 3α-diol effect. Biochemical determinations and histological examinations revealed an effect similar to castration after treatment with 3α-diol plus CA. After treatment with 3α-diol plus Oe2 plus CA fibromuscular stimulation as an oestrogen effect predominated in addition to glandular atrophy and metaplastic changes, especially in prostatic ducts. Epithelial hyperplasia is an effect of 3α-diol, whereas metaplastic proliferation only occurs in oestrogenized and androgenized dogs. In both types of prostatic enlargement CA prevents development of hyperplastic prostate.
STUDIES ON THE ORIGIN OF ALTERED THYROID HORMONE LEVELS IN THE BLOOD OF RATS DURING COLD EXPOSURE
Authors: van Hardeveld C. , Zuidwijk M. J. , Kassenaar A. A. H.
Published: December 2008

Rats were exposed to cold (4°C) for 1 and 4 weeks. The T4 plasma concentrations initially declined (24.5 ± 7.7 nmol/l) after 1 week but returned to normal levels after 4 weeks (52.9 ± 14.2 nmol/l). The T3 concentrations were elevated after both 1 and 4 weeks at 4°C (1.31 ± 0.21 and 1.38 ± 0.12 nmol/l, respectively). Control values (23°C) for T4 were 42.6 ± 10.3 and for T3 1.11 ± 0.13 nmol/l. Addition of 0.015 g KI/l to the drinking water prevented the T4 decrease in plasma after 1 week of cold exposure. No effect of iodide was observed at 23°C. The suppletion of KI did not change pattern of T3 increase after cold exposure. After 4 weeks of cold exposure the T4 levels of the iodide-supplemented animals did not differ from the non-supplemented group.

No evidence was found that increased food intake is a contributory factor in the development leading to increased T3 plasma levels during cold exposure.
REPLACEMENT ORAL ETHINYLOESTRADIOL THERAPY FOR GONADAL DYSGENESIS: GROWTH AND ADRENAL ANDROGEN STUDIES
Authors: Lucky Anne W. , Marynick Samuel P. , Rebar Robert W. , Cutler Gordon B. , Glen Michael , Johnsonbaugh Rober E. , Loriaux D. Lynn
Published: December 2008

We have studied growth and adrenal dehydroepiandrosterone (DHA) responses to iv synthetic adrenocorticotrophic hormone (ACTH, Cortrosyn) in 6 girls with gonadal dysgenesis before and during treatment with lowdose ethinyloestradiol (EOe2). In all patients there was a statisfactory induction of secondary sexual characteristics including increase in breasts and pubic hair and onset of withdrawal bleeding within 6 months of therapy. Height velocity increased from 2.8 ± 0.9 cm/year pre-treatment to 5.3 ± 1.5 cm/year (P < 0.02) in the first year. There was deceleration to 1.9 ± 1.1 cm/year in the second year. There was no disproportionate advancement in bone age and thus, presumably, no loss of ultimate height. We could demonstrate no change in basal or ACTH-stimulated levels of DHA, a specific adrenal androgen, to account for the increased pubic hair and growth in these patients.
RESTORATION OF OESTROGEN POSITIVE FEEDBACK EFFECT ON LH RELEASE BY BROMOCRIPTINE IN HYPERPROLACTINAEMIC PATIENTS WITH GALACTORRHOEA-AMENORRHOEA
Authors: Aono Toshihiro , Miyake Akira , Yasuda Takenori Shioji Motoi , Koike Koji , Kurachi Keiichi
Published: December 2008

Five mg of bromocriptine was administered for 3 weeks to 8 hyperprolactinaemic women with galactorrhoea-amernorrhoea, in whom the response of serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to 100 μg of iv LH-releasing hormone (LH-RH) had been evaluated. Twenty mg of conjugated oestrogen (Premarin®) was injected iv any day between the 10th and 12th day from the initiation of the treatment, and serum LH levels were serially determined for 120 h.

Hyperresponse of LH with normal FSH response to LH-RH was observed in most patients. Bromocriptine treatment for 10 to 12 days significantly suppressed mean (± se) serum prolactin (PRL) levels from 65.1 ± 23.0 to 10.4 ± 2.0 ng/ml, while LH (12.6 ± 2.1 to 24.8 ± 5.9 mIU/ml) and oestradiol (40.1 ± 7.6 to 111.4 ± 20.8 pg/ml) levels increased significantly. Patients on bromocriptine treatment showed LH release with a peak at 48 h after the injection of Premarin. The mean per cent increases in LH were significantly higher than those in untreated patients with galactorrhoea-amenorrhoea between 32 and 96 h after the injection.

The present results seem to suggest that the restoration of LH-releasing response to oestrogen following suppression of PRL by bromocriptine may play an important role in induction of ovulation in hyperprolactinaemic patients with galactorrhoea-amenorrhoea.
EFFECTS OF OBESITY, TOTAL FASTING AND RE-ALIMENTATION ON l-THYROXINE (T4), 3,5,3'-l-TRIIODOTHYRONINE (T3), 3,3',5'-l-TRIIODOTHYRONINE (rT3), THYROXINE BINDING GLOBULIN (TBG), CORTISOL, THYROTROPHIN, CORTISOL BINDING GLOBULIN (CBG), TRANSFERRIN, α2-HAPTOGLOBIN AND COMPLEMENT C'3 IN SERUM
Authors: Scriba Peter C. , Bauer Manfred , Emmert Dieter , Fateh-Moghadam Ahmed , Hofmann Gert G. , Horn Klaus , Pickardt C. Renate
Published: December 2008

The effects of total fasting for 31 ± 10 days followed by re-alimentation with an 800 calorie diet on thyroid function, i.e. T4,T3, rT3, RT3U (resin T3 uptake), and TSH, and on TBG levels in serum were studied sequentially in obese hospitalized patients (N = 18). Additionally, cortisol, growth hormone, prolactin, parathyrin and free fatty acids were followed as hormonal and metabolic parameters, respectively. Further, CBG, transferrin, α2-haptoglobin and complement C'3 were measured as representatives of other serum proteins.

Results before fasting: T4, T3,3, TBG, cortisol, CBG, α2-haptoglobin and complement C'3 of the obese patients were elevated when compared with healthy normal weight controls, whereas rT3, T4/TBG ratio, T3/TBG ratio, TSH, cortisol/CBG ratio, growth hormone, prolactin, parathyrin and transferrin of the obese group were normal. RT3U and fT4 index were decreased in the obese patients.

Results during fasting: Significant decreases were observed during fasting for the following parameters – T3, TBG, T3/TBG ratio, transferrin, α2-haptoglobin, complement C'3. rT3, T4/TBG ratio, RT3U, fT4 index and FFA increased. T4, TSH response to TRH stimulation, cortisol, CBG, cortisol/CBG ratio, parathyrin, growth hormone and prolactin did not change.

Results during re-alimentation: T3, TBG, T3/TBG ratio, TSH response to TRH, transferrin, α2-haptoglobin and complement C'3 increased. Conversely, rT3, RT3U, FFA, cortisol and cortisol/CBG ratio decreased, whereas the other parameters did not change.

Conclusions: 1) There is no evidence for primary hypothyroidism in obese patients during prolonged fasting and re-alimentation. 2) The rapid decrease of T3 and increase of RT3U after initiation of fasting are not fully explained by the observed slower decreases in TBG. 3) The alterations of T3, rT3 and RT3U resemble in their kinetics the changes in FFA levels. 4) Fasting reduced the levels of only certain serum proteins, interestingly TBG, transferrin, α2-haptoglobin and complement C'3, all of which, except transferrin, are elevated in obesity. 5) The magnitude of the observed decreases does not suggest any clinically relevant deficiencies in serum proteins. 6) Re-alimentation reverses rapidly all observed changes.
SUBCLINICAL HYPOTHYROIDISM IN ADDISON'S DISEASE
Authors: Faber Jens , Cohn Dorte , Kirkegaard Carsten , Christy Morten , Siersbæk-Nielsen Kaj , Friis Thorkild , Nerup Jørn
Published: December 2008

Fourteen patients with Idiopatic Addison's disease (IAD) were studied in order to detect a possible subclinical hypothyroid state. All were clinically euthyroid with normal serum thyroxine (T4) and serum 3,5′,3′-triiodothyronine (T3). Eleven had circulating thyroid microsomal antibodies in blood. The mean basal serum TSH was significantly higher than that of the control group but only three patients had values above the upper normal range. The mean value of serum T4 was decreased as compared to that of the normal persons, while serum 3,3′,5′-triiodothyronine was elevated. 7.5 mU bovine thyrotrophin per kilogram body weight injected intravenously caused a rise in serum T3 not different from the response in normals. However, as well increasing serum TSH as increasing microsomal antibody titer correlated significantly to decreasing thyroidal release of T3.

Our results suggest that clinically euthyroid patients suffering from IAD might have a beginning thyroidal insufficiency because of a progressive immunological damage of the thyroid.
PROSTAGLANDIN-STIMULATED LH RELEASE IN CYCLIC AND OVARIECTOMIZED RATS
Authors: Carlson J. C. , Kehl S. J.
Published: December 2008

The ability of prostaglandin (PG) E2 treatment to stimulate luteinizing hormone (LH) release was compared in cyclic (4-day) and ovariectomized rats. PGE2 (500 μg) was injected sc and plasma LH concentration was determined in serial jugular blood samples. Administration of PGE2 at 13.30 h on each day of the oestrous cycle resulted in a significantly greater increase in plasma LH levels at pro-oestrus and oestrus than at dioestrus 1 and 2. This differential response by the hypothalamo-hypophyseal axis during the oestrous cycle implicates regulatory activity by ovarian steroid feedback. In oestrogen-primed ovariectomized rats, PGE2 administration stimulated a significant increase in plasma LH, but similar treatment in non-primed castrates decreased plasma LH levels. This finding suggests a major role for oestrogen in regulating this response.
LH-SECRETORY RESPONSES CAUSED BY CONTINUOUS INFUSION OF LH-RH IN PSEUDOPREGNANT RATS
Authors: Koiter T. R. , Pols-Valkhof N. , Zürcher A. F. , Schuiling G. A.
Published: December 2008

The LH-secretory response (LH-S.R.), caused by (standard) infusion of LH-RH, was estimated throughout pseudopregnancy (PSP) as well as on dioestrus – 1 and –2 of the 4-day oestrous cycle. The LH-S.R. was judged according to 3 parameters: (1) mean maximal plasma LH concentration ("height", expressed in ng LH-RP-1/ml plasma), (2) mean area under the curve (AUC, expressed in "area units"), and (3) a composite, dimensionless, parameter: RQ ("response quotient"), defined as height/AUC. This latter parameter informs on the shape of the curve.

The LH-S.R.'s on day 1 of PSP and dioestrus-1 were both relatively low (about 350 ng LH-RP-1/ml plasma) and characterized by the same RQ about 12). On days 2, 5, 7 and 9 of PSP the LH-S.R.'s were essentially the same and appeared to have characteristics of the LH-S.R.'s of both PSP-1 and dioestrus-1 (RQ) and dioestrus-2 (height; about 1000 ng LH-RP-1/ml plasma). From day 10 on the LH-S.R.'s became increasingly higher (PSP 11: about 1900 ng LH-RP-1/ml plasma; PSP 12: about 3300 ng LH-RP-1/ml plasma) and steeper (RQ equals about 22).

At the end of PSP the spontaneous LH-surges were measured. These appeared to be very high if compared to those which are generated in 4-day cyclic rats (about 5800 ng LH-RP-1/ml plasma).

The results indicate that a period of PSP is not simply an ovulatory cycle of which the dioestrous phase is extended by about a week and it is suggested that "active" corpora lutea secrete, next to progesterone, substances which play a key role in the regulation of the secretion of LH in the course of PSP.
IMPAIRED CYCLIC-AMP RESPONSE TO THYROTROPHIN IN CONGENITAL HYPOTHYROIDISM WITH THYROGLOBULIN DEFICIENCY
Authors: Medeiros-Neto Geraldo A. , Knobel Meyer , Bronstein Marcello D. , Simonetti José , Filho Fadlo Fraige , Mattar Emilio
Published: December 2008

A 19 year old man had congenital hypothyroidism and severely retarded development. His thyroid gland was not enlarged and laboratory findings included low serum concentration of T4 (2.8 μg/100 ml) and T3 (16 ng/100 ml) with a high level of TSH (52 μU/ml) that rose to 192 μU/ml after TRH. 131I uptake by the thyroid was normal (41.5 % at 24 h) and did not show a normal increase after exogenous TSH administration (49.5 % at 24 h). The perchlorate discharge test was negative and no antibodies against thyroid antigens were found. Studies on the biopsy specimen revealed low iodide trapping by the thyroid slices and no formation of cyclic AMP after TSH was added to the medium. The endogenous TSH of the patient was biologically active increasing cyclic adenosine monophosphate c-AMP concentration in normal thyroid slices. No thyroglobulin was found in the thyroid tissue either by immunological or ultracentrifugational methods. An increased proportion of iodoalbumin was present in the serum. We postulate that the fundamental defect in this gland is an impaired generation of c-AMP by the defective thyroid cell and deficiency of thyroglobulin formation resulting in inadequate thyroxine and triiodothyronine synthesis.
ADENYL CYCLASE ACTIVITY IN HUMAN THYROID PLASMA MEMBRANES FROM NORMAL HUMAN THYROID TISSUE AND THYROID ADENOMAS
Authors: Wålinder O. , Karlsson F. A. , Dahlberg P. A.
Published: December 2008

The adenylcyclase (AC) activity of crude human thyroid plasma membranes were studied in some detail and conditions for optimal cyclic AMP-production established. Membranes from eight "cold" and two "hot" thyroid adenomas were investigated and compared to membranes from corresponding normal, paranodular tissues. The investigated membranes were found to contain similar basal AC activities, which were stimulated three to five times with TSH and 20–30 times with fluoride. Further, no difference in the TSH-sensitivity of AC from normal and "cold" adenomas could be detected. Thyrotrophin 0.02 mU/ml caused a measurable and 0.15 mU/ml a half-maximal stimulation of the cAMP-production. The data indicate, that disturbances of thyroid hormone production characteristic of thyroid adenomas, are not caused by alterations of the TSH-AC system and suggest that in a thyroid cell the degree of thyroid hormone synthesis do not alter the amount of plasma membrane-bound adenylcyclase.
LOW MOLECULAR WEIGHT INTRACELLULAR IODOCOMPOUNDS WITH LONG INTRATHYROIDAL HALF-LIFE: REMNANTS OF THYROGLOBULIN HYDROLYSIS?
Authors: Haeberli A. , Engler H. , von Grünigen C. , Kohler H. , Studer H.
Published: December 2008

in this paper additional information on low molecular weight, soluble, intrathyroidal iodocompounds with slow metabolic rate is provided. These compounds have previously been localized autoradiographically within the follicular cells.

Radioiodide was administered to rats on a normal iodine intake (6–7 μg/day) for 80 days to approach isotopic equilibration of the intrathyroidal iodine with the dietary radioiodide. When the isotope was omitted from the diet the intrathyroidal radioiodine was released with an apparent half-life of approximately 12 days. When the individual soluble components carrying radioiodine were analyzed after separation on Sephadex G-200, different apparent half-lives were found, the half-life of thyroglobulin (Tgb) being roughly 10 days and that of the low molecular weight iodocomounds being in the order of 60 to 100 days or more. In addition to the soluble low molecular weight iodocompounds, the radioactivity in the particulate fraction increased by 100 % during the tracer washout when compared to Tgb and the total soluble fraction.

The soluble slow turnover iodocompounds contained a higher percentage of carbohydrate and total iodine than Tgb, while the relative amounts of each sugar analyzed (hexoses, fucose, hexosamine and sialic acid) were close to those in Tgb. Sephadex G-25 chromatography of the low molecular weight iodocompounds obtained after Sephadex G-200 separation resulted in the separation of 4 peaks. Two peaks identified as iodopeptides could be further analyzed. The carbohydrate composition of these peptides was similar to that of 2 glycopeptides obtained after in vitro enzymatic hydrolysis of purified Tgb with pronase.

Slow equilibration with radioiodine, long apparent intrathyroidal half-life and carbohydrate content similar to that of Tgb, taken together with previously published data on intracellular localization of soluble intrathyroidal iodocompounds, suggest that the low molecular weight iodocompounds are products of in vivo hydrolysis of engulfed Tgb droplets.
URINARY EXCRETION OF CALCIUM, HYDROXYPROLINE AND 3′,5′-CYCLIC ADENOSINE MONOPHOSPHATE IN PRIMARY HYPERPARATHYROIDISM
Authors: Halse Johan , Gordeladze Jan O.
Published: December 2008

Urinary excretion of calcium (Ca), hydroxyproline (Hyp) and 3′,5′-cyclic adenosine monophosphate (cAMP) was measured during fasting, and in the afternoon, over a 3 day period. Twelve hyperparathyroid patients, of whom 6 were re-studied after successful parathyroid surgery, and 10 control subjects participated, and were maintained on a collagen free diet for the duration of the study.

Expressed as creatinine ratio values, Hyp was significantly higher in the morning than during the afternoon, whereas the Ca excretion pattern showed low morning and high afternoon values for all groups. cAMP excretion did not change during the two sampling periods.

Large day to day variations for each parameter were observed in the individual patient. The value of cAMP measurements in the diagnosis of primary hyperparathyroidism was confirmed. The results may imply that a diurnal variation in Hyp excretion exists in primary hyperparathyroidism and that food intake produces a suppression of Hyp excretion, possibly secondary to suppression of parathyroid function or, in our view, to increased calcitonin excretion.
EFFECT OF CYPROHEPTADINE ON THYROTROPHIN AND PROLACTIN SECRETION IN NORMAL MAN
Authors: Golstein J. , Vanhaelst L. , Bruno O. D. , L'Hermite M.
Published: December 2008

In order to investigate the effect of cyproheptadine, a compound with antiserotoninergic activity, on the secretion of thyrotrophin (TSH) and prolactin (PRL), the nocturnal secretory patterns of these hormones have been studied in 4 normal men in the basal state and after an oral treatment with the drug. In addition, the TSH and PRL responses to TRH of 6 women were compared in the basal conditions and after cyproheptadine treatment.

The TSH nocturnal secretion was slightly modified by drug treatment. The response to TRH as well as the basal levels were comparable in the treated and non-treated subjects. In contrast, the PRL secretion measured through the nocturnal investigation was significantly inhibited by cyproheptadine administration as were the PRL basal levels in the TRH test. The PRL response to TRH was comparable in both situations.
EFFECT OF GROWTH HORMONE AND PEPTIDE FRACTIONS CONTAINING SOMATOMEDIN ACTIVITY ON GROWTH AND CARTILAGE METABOLISM OF SNELL DWARFMICE
Authors: van Buul-Offers Sylvia , Van den Brande Jan Leo , Hoogerbrugge C. M. , Dumoleijn L. , v.d. Klundert P. L. M.
Published: December 2008

In order to obtain more information about a possible role of somatomedin (SM) in vivo, increase in length and weight, costal cartilage activity (35SO4 = and 3H-methyl-thymidine incorporation), organ weight and serum glucose levels were studied in Snell dwarfmice, during treatment with human growth hormone (hGH), l-thyroxine (T4), insulin and a semipurified SM-preparation (SM-P1).

SM-P1, hGH and T4 caused a significant increase in length and weight, whereas insulin was not effective in a dosage similar to the insulinlikeactivity of the SM-P1 preparation measured by radioreceptorassay. The effect obtained with the SM-preparation cannot be due to contamination of GH, prolactin, T4, insulin or testosterone.

Costal cartilage activity was measured three days after initiation of treatment by incubation immediately after sacrifice in plasma free medium. Both sulphate and thymidine incorporation were increased by the administration of SM-Pl and hGH, compared to buffer treated controls. After treatment for four weeks no differences between treated and untreated animals in cartilage activity could be observed anymore.

Both SM-P1 and hGH induced weight gain in most organs. An outspoken effect was seen on lymphoid organs, the submandibular salivary glands and muscle, a sizable effect was present on the kidneys and a small effect, not reaching significance for the SM-Pl treated group on brain weight.

An impression of divergence was seen with liver weight, which increased on hGH while there was a small and not significant rise on SM-P1. A definite discrepancy was found in skinfold thickness, which was essentially unchanged on hGH and increased on SM-P1. Testes and epididymal fat, though probably increasing their weights, were in insufficient number to do statistics on.

Serum T4 is low in untreated dwarfmice. It is increased to a subnormal level after hGH administration whereas no effect is observed with SM-P1. The dose dependent effect of insulin, measured by radioimmunoassay, on the induction of hypoglycaemia is markedly similar to the effect of nonradioimmunoactive insulin-like activity of SM-P1 as measured by radioreceptorassay. The hypoglycaemia induced with insulin and the SM-preparation is reduced by adding 10 % glucose to the diet.

In conclusion: SM-P1 shows growth stimulating and insulin-like actions in vivo. The pattern of effects obtained with hGH, T4 and insulin differs from that of SM-P1.
KLINEFELTER'S SYNDROME: EFFECTS OF OESTROGEN ON GROWTH HORMONE, PROLACTIN AND THYROTROPHIN RELEASE, AND ON THYROTROPHIN AND PROLACTIN RESPONSES TO THYROTROPHIN-RELEASING HORMONE
Authors: Barbarino Antonino , De Marinis Laura
Published: December 2008

In 4 normal men and 8 patients with Klinefelter's syndrome the effects of oestradiol-17 β (15μg/kg daily for 8–13 days) on serum levels of pituitary hormones were investigated. Control levels of gonadotrophins in the Klinefelter patients were significantly higher than in the normal males, whereas serum testosterone (T) levels were lower. Oestradiol induced a decrease in serum gonadotrophin concentrations in both the control subjects and the Klinefelter patients, whereas a testosterone suppression was observed in the normal subjects, but not in the Klinefelter patients. Control serum growth hormone (hGH), and prolactin (hPRL) levels were of comparable magnitude in both groups and significantly increased during oestradiol administration. Serum thyrotrophin (TSH) levels were normal before and during oestrogen treatment. Basal serum oestradiol levels were within the normal male range, and were increased during treatment. Prolactin and thyrotrophin responsiveness to TRH stimulation was examined in Klinefelter patients before and during oestrogen administration. Before treatment, hPRL responses to TRH were higher than those observed in normal men. During oestrogen treatment hPRL responses to TRH were significantly increased when compared to those observed before treatment. TSH responses to TRH were normal both before and during treatment.

These studies indicate that in patients with Klinefelter's syndrome pharmacological doses of oestrogen induce different effects on the hypothalamic-pituitary axis, as regards the release of gonadotrophins, prolactin, thyrotrophin, and growth hormone, similar to those observed in normal men. This fact supports the conclusion that in Klinefelter's syndrome the abnormality in the pituitary-gonadal feedback mechanism is selectively confined to the testosterone feedback control of gonadotrophin secretion. Finally, in patients with Klinefelter's syndrome, oestrogen is capable of inducing a significant increase of the hPRL response to TRH stimulation.
FURTHER STUDIES ON HYPOTHALAMIC-PITUITARY-TESTICULAR FUNCTION IN OLD RATS
Authors: Pirke Karl M. , Krings Beate , Vogt Hermann-J.
Published: December 2008

The dysfunction of the hypothalamic-pituitary-gonadal axis in old age was studied in 24-month old male Wistar rats which were compared with 3-month old animals. The hypothalamic LH-RH content and the pituitary LH were significantly lower in the old than in the young adult animals. The plasma concentrations of LH and testosterone were significantly higher in the young rats. The primary cause of these age-dependent changes probably is a hypothalamic dysfunction. When isolated Leydig cells of young and old rats were incubated in vitro, the testosterone secretion per cell was significantly smaller in old than in young cells with as well as without HCG stimulation.

In vivo stimulation of rats by iv injection of biologically active iodinated hCG revealed that the intratesticular uptake of the gonadotrophin was not different in young and old rats. The testosterone response, however, was significantly reduced in old age. An in vitro "desensitisation" experiment in which the LH receptor capacity was artificially reduced demonstrated that the 40 % reduction of receptor capacity in old testes as described earlier will not impair the testicular uptake of gonadotrophin from blood. Repeated injection of hCG results in equally elevated testosterone concentrations in young and old rats.
PERSISTING SUPPRESSION OF PROLACTIN SECRETION AFTER LONG-TERM TREATMENT WITH BROMOCRIPTINE IN PATIENTS WITH PROLACTINOMAS
Authors: Eversmann T. , Fahlbusch R. , Rjosk H. K. , von Werder K.
Published: December 2008

The effect of bromocriptine withdrawal after long-term treatment on prolactin levels has been investigated in thirty-seven patients with prolactinomas. In ten patients with macroprolactinomas and post-operatively excessively high prolactin levels persisting suppression of prolactin secretion after bromocriptine withdrawal has been observed. This effect was not observed in patients with microprolactinomas or macroprolactinomas with only moderately elevated prolactin levels. The degree of persisting suppression correlated to the height of prolactin levels before treatment and to the duration of bromocriptine therapy. No correlation was found between the rise of prolactin levels after bromocriptine withdrawal and withdrawal time. It is suggested that the persisting suppression of prolactin levels is a sequence of reduction in tumour size. This anti-proliferative action of bromocriptine seems to be specific for the prolactin secreting cells in macroprolactinomas with high proliferation rate and high prolactin turn-over. These findings offer new possibilities in the management of patients with macroprolactinomas.
EFFECT OF THE NORETHISTERONE MINIPILL ON THE PLASMA LEVELS OF BIOLOGICALLY AND IMMUNOLOGICALLY ACTIVE LUTEINIZING HORMONE IN WOMEN
Authors: Balogh A. , Robertson D. M. , Diczfalusy E.
Published: December 2008

The relationship between biologically and immunologically active luteinizing hormone (LH) in plasma was investigated daily throughout a menstrual cycle in 29 women before and during the second month of the oral administration of norethisterone (Mini-Pe®, Astra-Syntex) in a daily dose of 0.3 mg. The biological activity was determined by an in vitro bioassay and the immunological activity by a radioimmunoassay method. A characteristic midcycle surge of LH was observed with both assay methods in all 29 control cycles. Of the 29 treatment cycles studied with both assay methods, 10 cycles exhibited a similar LH pattern, although the levels of both activities were significantly depressed (P < 0.001) during all phases of the cycle. The biological to immunological (B/I) ratios of plasma LH between the treatment and control cycles were not significantly different.

Of the remaining 19 treatment cycles, in which no "midcycle" LH peak was evidenced, the levels of both activities in the treatment periods were significantly lower (P < 0.05) than in the follicular phase and significantly higher than in the luteal phase (P < 0.05) of the control cycles. The overall B/I ratios were significantly lower in the treatment periods than in the control cycles (P < 0.001). However, the influence of this difference on the general pattern of immunological activity in comparison with that of biological activity was relatively small.

It is concluded that the irregular patterns of immunological hLH activity which are observed after treatment with low doses of norethisterone are similar to those of the biological activity.
THE INFLUENCE OF OESTROGEN ADMINISTRATION IN VIVO ON IN VITRO PROLACTIN RELEASE
Authors: Jaques Sandford , Gala Richard R.
Published: December 2008

The influence of oestrogen administered to the ovariectomized rat on the interaction between dopamine (DA) and thyrotrophin releasing hormone (TRH) on the release of radioimmunoassayable (RIA) and [3H] leucine incorporated into prolactin ([3H]PRL) was examined in vitro. Dopamine had a more marked suppressing effect on newly synthetized PRL (80 %), as determined [3H]PRL, than on total PRL (50 %), as determined by RIA-PRL. The administration of 5 μg of oestradiolbenzoate (OeB) for 7 days resulted in blocking the suppressing effect of DA when RIA-PRL was measured but not when [3H]PRL was measured. The administration of 5 μg of OeB enabled TRH to partially override the suppressing effect of DA and the degree of response was more marked when RIA-PRL was measured than when [3H]PRL was measured. The administration of 50 μg of OeB for 3 days enabled TRH to override the DA blockade of prolactin release to levels comparable to that of the control when RIA-PRL was measured but had little to no effect on [3H]PRL. The results are discussed in relation to the two storage pools of PRL in the pituitary and the data suggest that DA acts predominantly to suppress the newly synthetized, rapidly releasable pool. Oestrogen acts to block DA action on the older more stable PRL pool. The ability of TRH to override the DA blockade of PRL release depends upon the presence of oestrogen; here TRH acts predominantly on the older more stable pool of PRL. Oestrogen's action on disrupting the DA suppression of PRL release appears to be related to the time of day the hormone is administered subsequent to when the pituitary is exposed to DA in vitro.
THE EFFECTS OF TETRAIODOTHYROACETIC AND TRIIODOTHYROACETIC ACIDS ON THYROID FUNCTION IN EUTHYROID AND HYPERTHYROID SUBJECTS
Authors: Burger A. G. , Engler D. , Sakoloff C. , Staeheli V.
Published: December 2008

The effects of tetraiodothyroacetic (Tetrac) and triiodothyroacetic acids (Triac) on thyroid function have been investigated in euthyroid and hyperthyroid subjects. 50, 100, 200, 400 or 800 μg of Triac were administered to 8 euthyroid volunteers three times (tds) over a 24 hour period. 3 × 800 μg Triac/24 h was sufficient to cause a significant reduction in serum T3. Tetrac, given as an iv bolus of 3600 μg, produced a sustained reduction in serum T3 for up to 4 days after the injection. Intermediate doses of Tetrac (1200 μg) or Triac (400 μg tds) significantly reduced the TSH response to TRH (66 % and 43 % respectively).

Seven hyperthyroid patients received Triac 200 μg tds for 2 days, and in 2, a rapid decrease in serum T3 was seen. Similar changes in serum T3 were also produced with iodide administration.

The results suggest that 1) in euthyroidism, Tetrac and Triac act directly at the pituitary level to inhibit the TSH response to TRH; 2) in some cases of hyperthyroidism, Triac produces a block in T3 secretion by virtue of the iodide produced by its metabolism.
FAILURE OF METOCLOPRAMIDE TO INFLUENCE LH, FSH AND TSH SECRETION OR THEIR RESPONSES TO RELEASING HORMONES
Authors: Spitz Irving M. , Trestian Stefan , Cohen Haim , Arnon Naomi , LeRoith Derek
Published: December 2008

Intravenous metoclopramide (MET) (10 mg) induced a brisk PRL response with a mean ± sem peak of 85.3 ± 7.7 ng/ml maximal at 30 min. l-Dopa, but not atropine pre-treatment, attenuated the prolactin (PRL) response to MET. This indicates that the antidopaminergic properties of MET mediate PRL secretion. MET did not influence basal levels of TSH, LH or FSH. Neither did it affect their response to the respective releasing hormones. Our results indicate that dopaminergic blockade induced by iv MET, does not influence the secretion of the pituitary glycoprotein hormones.
THYROTROPHIN-RESPONSIVE ADENYLATE CYCLASE ACTIVITY IN THYROID TOXIC ADENOMA
Authors: Toccafondi Roberto S. , Rotella Carlo M. , Tanini Annalisa , Fani Patrizia , Arcangeli Paolo
Published: December 2008

The adenylate cyclase system was studied in hyperfunctioning autonomous nodules in comparison with normal thyroid tissue. The basal, TSH- and NaF-stimulated adenylate cyclase activities were tested in purified plasma membrane preparations. Basal enzyme activity in membranes from hyperfunctioning nodules was variable and the response to TSH was either normal, low or absent. The present study demonstrates that an intact adenylate cyclase activity, hyporesponsive to TSH, may exist in the cell membrane of the adenoma.