bluuebunny/crossref_metadata_2025 huggingface dataset:
17β‐HYDROXYSTEROID DEHYDROGENASE AND AROMATASE ACTIVITY IN BREAST FAT FROM WOMEN WITH BENIGN AND MALIGNANT BREAST TUMOURS
Authors: BERANEK P. A. , FOLKERD E. J. , GHILCHIK M. W. , JAMES V. H. T.
Published: March 2008

The activity of 17β‐hydroxysteroid dehydrogenase and aromatase was studied in adipose tissue taken from women aged between 22 and 83 years with benign or malignant breast lesions. The benign and malignant groups showed no significant differences in the mean activities of either of the enzymes studied. Under the experimental conditions used, the rate of conversion of oestrone to oestradiol varied markedly between subjects (6‐169 ng oestradiol/mg protein/h), and there was a positive correlation between oestrone reduction and the total body weight of the tissue donor. In contrast, although the apparent Km for oestradiol (0·1–2·6 μmol/1) was lower than that for oestrone (9–14 μmol/1) the maximum velocity for oestrone production was very low (10–50 pmol/mg protein/h), and there was no obvious correlation with the age or body weight of the tissue donor. Aromatase activity in breast fat was at the lower end of the normal range of activity previously reported for abdominal adipose tissue, and there was no correlation between oestrone production and age or body weight.
INCREASED PLASMA CONCENTRATION OF N‐TERMINAL β‐LIPOTROPHIN AND UNBOUND CORTISOL DURING PREGNANCY
Authors: ABOU‐SAMRA A. B. , PUGEAT M. , DECHAUD H. , NACHURY L. , BOUCHAREB B. , FEVRE‐MONTANGE M. , TOURNIAIRE J.
Published: March 2008

The plasma concentration of N‐terminal β‐lipotrophin (β‐LPH), total and protein unbound cortisol, progesterone and the transcortin (CBG) binding parameters have been measured in 21 women in the early follicular phase and in 70 pregnant women at various stages of pregnancy. Results showed that the plasma CBG binding capacity and the concentrations of total cortisol and progesterone increased significantly at each trimester of pregnancy while the plasma concentration of unbound cortisol increased significantly only in the 2nd and the 3rd trimesters of pregnancy. In addition, a significant increase of N‐terminal β‐LPH level was observed during the 3rd trimester. By chromatography, it is demonstrated that during the 3rd trimester of pregnancy the β‐LPH/γ‐LPH molar ratio decreases dramatically and that the increase of N‐terminal β‐LPH concentration is mainly due to a two fold increase in γ‐LPH concentration.
IN VITRO GENERATION OF NADPH AS AN INDEX OF THYROID STIMULATING IMMUNOGLOBULINS (TGI) IN GOITROUS DISEASE
Authors: McMULLAN N. M. , SMYTH P. P. A.
Published: March 2008

A quantitative cytochemical assay for the measurement of total NADPH formation in guinea pig thyroid tissue following incubation with thyroid stimulators was validated and applied to the measurement of such stimulators in IgG concentrates prepared from human plasma. Pentose shunt enzyme activity was not uniformly distributed in thyroid tissue but this could be overcome and NADPH generation in such tissue used to assess accurately thyroid stimulators if a sufficient number of thyroid cells were measured. Specificity studies showed that antiserum to human IgG significantly diminished the NADPH generating capacity of IgG concentrates prepared in plasma from goitrous patients while antiserum to h‐TSH had no such effect. The measurement of thyroid growth stimulating immunoglobulins (TGI) depended not only on the amount of NADPH generated but also on the IgG concentration at which maximum responses occurred. TGI present in goitrous GRAVES' disease were 10 times more potent than those present in euthyroid goitre, while such stimulators when present in toxic nodular goitre appeared to possess an intermediate potency. This finding, when taken together with the demonstration that TSH stimulation decreased intercellular differences in pentose shunt activity, provides experimental evidence for the hypothesis that an acute intense growth stimulus affecting all thyroid cells produces the diffuse hyperplasia characteristic of GRAVES' disease. In contrast, the weaker stimulus observed in nodular goitre may, over a period of time, result in the asymmetric hyperplasia commonly observed in this condition.
ENDEMIC INFANTILE HYPOTHYROIDISM IN A SEVERE ENDEMIC GOITRE AREA OF CENTRAL AFRICA
Authors: VANDERPAS J. , BOURDOUX P. , LAGASSE R. , DRAMZAIX M. , LODY D. , NELSON G. , DELANGE F. , ERMANS A. M. , THILLY C. H.
Published: March 2008

Thyroid function and exposure to dietary goitrogenic factors (iodine deficiency and thiocyanate overload) were studied at birth and from birth to 7 years in 200 neonates and 347 children living in the severe endemic goitre area of Ubangi, Northern Zaire. Serum T4 was at the lower limit of normal at birth (104 ± 4 nmol/1) and stayed at that level during the first year of life (123 ± 9) (NS), but decreased to 75 ± 8 (P < 0·001) at 2–4 years and to 62 ± 6 (P < 0·001) at 5–7 years of age. Mean serum FT4 decreased from 10·4 ± 0·9 pmol/1 during the first year to 8·2 ± 1·0 (NS) at 2–4 years (NS) and to 7·7 ± 0·9 (P < 0·05) at 5–7 years. Mean serum TSH was 10·4 (8·4‐12·9) m U/1 (geometric mean ± 1 SEM) during the first year, 10·1 (7·5‐13·7) (NS) at 2–4 years and 24·3 (18·5–31·9) (P < 0·05) at 5–7 years. Mean serum T3 was 3·23 ± 0·12 nmol/1 during the first year and remained stable thereafter. The frequencies of low T4 (T4 < 77 nmol/1), high TSH TSH (TSH > 50 mU/1), and low T4 and T3 (T3 < 1·69 nmol/l) were twice as high at 5–7 years as in the first year (respectively 65%, 42% and 15%). The urinary iodide concentration of the children was stable and low throughout the study period. By contrast, serum thiocyanate concentration which was high at birth (129 ± 5 ųmol/1) decreased to normal values between 3 and 12 months of age and increased again during and after weaning (1 to 3 years of age) to reach a value of 138 ųmol/l which was comparable to that observed in adults in the same area. Thiocyanate concentration was high (133 ± 7 ųmol/l) in the mothers' serum but low in the mothers' milk (57 ± 3 ųmol/1) (P < 0·01). Multivariate analysis
MEASUREMENT OF FREE THYROXINE AND FREE TRIIODOTHYRONINE IN ASYMPTOMATIC SUBJECTS WITH HIGH CONCENTRATIONS OF SERUM TSH AND A HISTORY OF RADIOIODINE THERAPY
Authors: FRANKLYN J. A. , SHEPPARD M. C. , RAMSDEN D. B. , HOFFENBERG R.
Published: March 2008

Total and free thyroid hormones were measured in a group of asymptomatic subjects with high circulating TSH concentrations and a previous history of radioiodine therapy. Subjects in the high TSH group all fell within the normal range for measurements of total T4, total T3 and T4/TBG ratio. Concentrations of free T4 or free T3 were below the normal range in more than half (9 out of 17) of the high TSH group suggesting that these measurements are more sensitive indices of thyroid failure than measurement of total hormones or T4/TBG ratio.

Hypothyroidism is a common complication of the treatment of thyrotoxicosis with radioiodine, the cumulative incidence 15 years after treatment reaching 80% in some centres (Greig, 1973). Although considered a good index of impaired thyroid function, a high serum TSH is commonly observed after radioiodine therapy and may persist for some years in subjects judged euthyroid by other criteria (Toft et al., 1975). We have recently demonstrated the value of measurements of free T4 and free T3 in the routine diagnosis of thyroid dysfunction (Franklyn et al., 1984) and in the present study we have compared these measurements with other parameters of thyroid function in a group of asymptomatic subjects with high circulating TSH concentrations and a history of radioiodine therapy.
PULSATILE RELEASE OF LH AND OESTRADIOL DURING THE PERIOVULATORY PERIOD IN WOMEN
Authors: DJAHANBAKHCH O. , WARNER P. , MCNEILLY A. S. , BAIRD D. T.
Published: March 2008

Blood was collected every 8 h in five women from Day 10 of the menstrual cycle for 5–7 d for the measurement of LH, oestradiol and progesterone. In all women the LH surge started between 2400 and 0800 h before there was any significant decline in the concentration of oestradiol. In order to investigate the pulsatile secretion of LH and estradiol during the mid‐cycle surge, blood samples were collected every 5 min for up to 5 h. Immediately before and during the LH surge there were numerous episodic pulses of LH with an interpulse interval (44 ± 7 min) very similar to that observed in two women with hypergonadotrophic hypogonadism (48 min). The concentration of oestradiol fluctuated in a similar manner although it was not always possible to relate each pulse of oestradiol to a corresponding pulse of LH. The mid‐cycle surge of LH is characterized by frequent pulses of high amplitude. These results are compatible with the view that the positive feedback effect of oestradiol is due not only to enhanced sensitivity of the anterior pituitary to LHRH but also to the high frequency of LHRH pulses released from the hypothalamus.
THE INHIBITION BY ETOMIDATE OF THE 11β‐HYDROXYLATION OF CORTISOL
Authors: FRY D. E. , GRIFFITHS H.
Published: March 2008

The effect of a sleep‐dose of etomidate on the plasma concentrations of cortisol, 11‐deoxycortisol and 17αOH‐progesterone was investigated in eight patients; two other patients received thiopentone. Blood samples were collected at 0, 15 and 30 min after etomidate or thiopentone when an injection of tetracosactrin was given and a final sample was collected at 60 min. The plasma cortisol response to tetracosactrin was depressed below normal in patients given etomidate, and the 11‐deoxycortisol response was very high, ranging from 36·4 to 184·7 nmol/1. The two patients that received thiopentone had a normal response to all steroids. The identity of the plasma 11‐deoxycortisol in two patients was confirmed by high‐performance liquid chromatographic separation and quantification by both spectrophotometric and radioimmunoassay measurements. These results suggest that a single dose of etomidate inhibits 11β‐hydroxy]ation of cortisol.
EVIDENCE FOR DECREASED ENDOGENOUS DOPAMINE AND OPIOID INHIBITORY INFLUENCES ON LH SECRETION IN POLYCYSTIC OVARY SYNDROME
Authors: CUMMING D. C. , REID R. L. , QUIGLEY M. E. , REBAR R. W. , YEN S. S. C.
Published: March 2008

The inhibitory role of the dopaminergic and opioidergic mechanisms in the control of LH secretion in patients with polycystic ovary syndrome (PCO) was evaluated. The administration of an opiate receptor antagonist, naloxone, of a dopamine receptor antagonist, metoclopramide, or of human synthetic βh‐endorphin, were unable to alter LH secretory activity in patients with PCO. Since identical doses of these antagonists and the opiate agonist have elicited respectively a rise and fall of LH levels in normal cycling women, these findings suggest that an underlying hypothalamic component of defect in endogenous dopamine and opioid control may be responsible for the inappropriate gonadotrophin secretion in this syndrome.
DIURNAL PROLACTIN CHANGES IN HUMAN CEREBROSPINAL FLUID
Authors: BARRECA T. , PERRIA C. , FRANCESCHINI R. , SIANI C. , MESSINA V. , FRANCAVIGLIA N. , ROLANDI E.
Published: March 2008

Eight adult male patients suffering from hydrocephalus of differing aetiologies were investigated in order to detect the existence of diurnal variations of prolactin (PRL) concentration in human cerebrospinal fluid (CSF). Blood and ventricular CSF samples were taken every 2 h during the day (0800–2200 h) and every hour during the night (2300–0700 h). CSF mean PRL levels showed significant nyctohemeral variations with low levels (2·1 ± 0·3 ng/ml) during day‐time and higher levels at night (3·3 ± 0·1 ng/ml), similar to that observed in serum (PRL values: 16·4 ± 5·2 and 24·8 ± 4·3 ng/ml during day and night periods respectively). The presence of a 24 h CSF PRL secretory profile similar to that in serum was shown in six patients with normal 24 h mean PRL values and normal diurnal changes in serum. In two patients with an altered serum 24 h secretory pattern no significant nyctohemeral variations in CSF PRL levels were found. Present data show the existence in man of nyctohemeral variations in CSF PRL content related to the 24 h changes of PRL levels in serum.
THE THYROID FUNCTION IN YOUNG MEN DURING PROLONGED EXERCISE AND THE EFFECT OF ENERGY AND SLEEP DEPRIVATION
Authors: OPSTAD P. K. , FALCH D. , ØKTEDALEN O. , FONNUM F. , WERGELAND R.
Published: March 2008

Thyroid function has been investigated in 24 young military cadets participating in a 5 d ranger training course with heavy physical excercise, calorie deficiency and deprivation of sleep. The cadets were divided into three groups, each differing in the amount of sleep and food consumption. The serum levels of thyroid hormones (T4, FT4, T3, rT3) and TBG showed a biphasic pattern during the course. Initially there was an increased secretion concomitant with an increased deiodination of T4 to T3 and rT3 mainly due to physical exercise. When the activities lasted for several days without sufficient food supply the thyroid secretion decreased simultaneously with an alteration of the peripheral conversion of T4 to rT3 instead of T3. A significant correlation was found between the changes in total and free thyroxine (r= 0·9) and between the increase in rT3 and decrease in T3 (r= 0·6). TSH decreased during the first day of activities and remained low throughout the course. The TSH response to TRH stimulation was greatly reduced during the course due to physical exercise and calorie deficiency. The present investigation demonstrates that the thyroid function is strongly affected by prolonged physical exercise and a negative energy balance, whereas sleep deprivation does not have any significant influence. The results indicate that the alteration observed is not regulated just by the hypothalamo‐pituarity‐thyroid‐axis alone.
DISSOCIATION OF ADRENARCHE AND GONADARCHE IN DIABETES MELLITUS
Authors: COHEN H. N. , PATERSON K. R. , WALLACE A. M. , BEASTALL G. H. , MANDERSON W. G. , MacCUISH A. C.
Published: March 2008

Serum concentrations of testosterone and dehydroepiandrosterone sulphate (DHAS) have been measured in 10 stable insulin‐dependent diabetic (IDD) males (chronological age (CA) range 13·0‐17·5 years). Their results have been compared with those of a control population of 69 non‐diabetic males who presented with mild constitutional growth delay and whose skeletal maturity and pubertal development were similar to the diabetic subjects. Within bone ages (BA) 11·0–14·5 years no significant difference was observed between the serum testosterone concentrations of the diabetic patients and controls: diabetic males, 8·2 (0·3–25) nmol/1 (median and range); controls, 7·0 (< 0·3–23) nmol/1. In contrast, within BA 11·0–14·5 years, the diabetic males had significantly lower serum DHAS concentrations: diabetic males, 1·1 (0·7–4·2) μmol/1; controls, 3·7 (0·7–5·6) μmol/1 (P < 0·001). The serum DHAS concentrations of the diabetic males were also significantly lower than the controls when matched separately for pubic hair and genital development, testicular volume and serum testosterone, (in each comparison P < 0·02). Serum DHAS concentrations of the diabetic males did not correlate significantly with CA, BA, BA delay (CA‐BA), age of onset of diabetes, duration of diabetes, or glycosylated haemoglobin (GHb), but significant correlation was observed between BA delay and duration of diabetes, r= 0·65, P < 0·05. We conclude that gonadarche appears to proceed despite delayed adrenarche in IDD males. This study presents further evidence in favour of adrenarche and gonadarche being independent physiological events. The causes and clinical significance of low serum DHAS concentrations in adolescent diabetic males remain to be established.
DIFFERENTIAL DIAGNOSIS BETWEEN HYPOTHALAMIC AND PITUITARY hGH DEFICIENCY WITH THE AID OF SYNTHETIC GH‐RH 1–44
Authors: LARON Z. , KERET R. , BAUMAN B. , PERTZELAN A. , BEN‐ZEEV Z. , OLSEN D. B. , COMARU‐SCHALLY A. M. , SCHALLY A. V.
Published: March 2008

Synthetic GH‐RH 1–44 administered as an intravenous bolus (1 μg/kg) evoked a marked hGH rise (>20 ng/ml) in three children with constitutional short stature and in two of eight children diagnosed as having hGH deficiency by insulin hypoglycaemia and/or clonidine tests. As judged by the intensity of the hGH response to the dose employed and the peak time, GH‐RH 1–44 may be as potent as GH‐RH 1–40 in children. It is concluded that GH‐RH is an important addition to the endocrine armamentarium, providing the means for differentiation between hypothalamic and pituiary hGH deficiency in a simple test which is devoid of side effects.
A CYTOCHEMICAL SECTION BIOASSAY FOR PLASMA TRILOSTANE: AN ORALLY ACTIVE INHIBITOR OF 3β‐HYDROXYSTEROID DEHYDROGENASE ACTIVITY
Authors: EARNSHAW R. J. , MITCHELL R. , ROBERTSON W. R.
Published: March 2008

Trilostane is a competitive inhibitor of 3β‐hydroxysteroid dehydrogenase activity in vitro and an orally active inhibitor of steroidogenesis in vivo. A cytochemical section bioassay for this drug (4α, 5‐epoxy‐17β‐hydroxy‐3‐oxo‐5α‐androstane‐2α‐carbonitrile) in human plasma has been developed. The assay is based upon the inhibition of 3β‐hydroxysteroid dehydrogenase (3β‐HSD) activity in the corpus luteum of unfixed tissue sections (6 μm) of the mature dioestrous rat ovary. Trilostane is extracted from plasma by a simple chloroform procedure. The stanuard curve (0·15–2·5 μmol/I pure trilostane) exhibits a four‐fold change in 3β‐HSD activity and is constructed in the presence of extract from control plasma pools. The detection limit of the plasma assay is 2μmol/I trilostane after allowing for dilution effects and recovery losses. This level gives a significantly different response from the zero quality control (P<0·05) and has an inter‐assay coefficient of variation of < 15%. No false positives have been recorded to date and the majority of samples from subjects receiving therapeutic doses of the drug have levels of > 2 μmol/1. Intra‐ and inter‐assay coefficients of variation using both plasma quality controls and unknown samples are 4% (n= 15) and 13·9% (n= 27) respectively. Recovery is 80·9% (n= 13) and 79·10% (n= 10) for plasma quality controls containing 12 and 4·8 μmol/1 trilostane respectively. Dilutions (up to 1:5) of plasma extracts are parallel to the standard curve and the assay throughput is approximately 16 samples/week technician. Testosterone, oestradiol, oestriol, dehydroepiandros‐terone (DHEA), DHEA‐sulphate, progesterone, cortisol, androstenedione and dexamethasone (all at 1 μmol/1) were without effect on the 3β‐HSD assay. It is concluded that the bioassay is suitable for assaying trilostane in human plasma.
ALTERATION OF HORMONE LEVELS IN NORMAL MALES GIVEN THE ANABOLIC STEROID STANOZOLOL
Authors: SMALL M. , BEASTALL G. H. , SEMPLE C. G. , COWAN R. A. , FORBES C. D.
Published: March 2008

Anabolic steroids have widespread metabolic effects but, to date, their proven clinical indications have been limited. Recently the 17 α‐alkylated steroid, stanozolol, has been shown to be of value in a variety of commonly occurring vascular diseases. Its endocrine effects have received little attention and we have investigated the effect of administering a 14 d course of stanozolol (10 mg orally per day) on a variety of important hormonal pathways in nine healthy male subjects. Significant changes occurred as follows: a 55% reduction in serum testosterone levels was noted and was accompanied by reductions in ‘derived’ free testosterone, sex hormone binding globulin and LH levels; total T4 and T3 levels fell in association with a decrease in thyroxine binding globulin, but no alteration was detected in TSH or free T4 levels. Changes in vitamin D status, with falls in 25‐hydroxycholecalciferol and vitamin D binding globulin were also observed. These effects were reversible on stopping treatment. Stanozolol therapy therefore leads to a number of hormonal changes, probably by an action at both pituitary and hepatic levels.
GONADOTROPHIN RESPONSES TO GnRH IN PRECOCIOUS PUBERTY TREATED WITH GnRH ANALOGUE
Authors: DONALDSON M. D. C. , STANHOPE R. , LEE T. J. , PRICE D. A. , BROOK C. G. D. , SAVAGE D. C. L.
Published: March 2008

The gonadotrophin releasing hormone analogue Buserelin was given by intranasal spray to 13 children with precocious puberty. The LH responses to GnRH reverted to prepubertal levels in the boys on 200–400 μg daily of the analogue while doses of 400–1200 μg daily were needed to suppress the girls. The significance of this apparent sex difference is uncertain.
THE RESPONSE OF NORMAL SUBJECTS AND PATIENTS WITH IDIOPATHIC GROWTH HORMONE DEFICIENCY TO CONTINUOUS INFUSION OF HUMAN PANCREATIC GROWTH HORMONE RELEASING FACTOR 1–44
Authors: DAVIES R. R. , TURNER S. J. , PARKIN J. M. , JOHNSTON D. G.
Published: March 2008

The GH response to a prolonged continuous infusion of human pancreatic growth hormone releasing factor (hpGRF 1–44), 0.3 μg/kg/h was evaluated in seven patients with severe idiopathic GH deficiency, one patient with partial deficiency and in seven normal controls. Normal controls had a multiphasic response with a first peak between 15 and 90 min of 13.6 to 88.5, mean 45.6 mU/l and a second peak between 105 and 195 min of 8.8 to 73.1, mean 33.8 mU/l. However, the magnitude and pattern of response were highly variable. Six of the seven patients with severe GH deficiency had a response with a maximum level between 30 and 90 min of 3.3 to 7.5, mean 4.8 mU/l. Mean levels remained greater than 2.0 mU/l throughout the infusion but further peaks were absent or minimal. The patient with partial GH deficiency responded in a normal manner. hpGRF 1–44 by continuous infusion thus induced GH release in seven of eight patients with idiopathic GH deficiency though the response was impaired and the pattern of secretion abnormal in severely deficient patients.
THYROREGULATORY CHANGES ASSOCIATED WITH SMOKING IN 70‐YEAR‐OLD MEN
Authors: EDÉN S. , JAGENBURG R. , LINDSTEDT G. , LUNDBERG P. ‐A. , MELLSTRÖM D.
Published: March 2008

In a previous study we have analysed serum free T4 concentrations in a representative population of 70‐year‐old men. In the present study the effect of previous or present tobacco smoking on free T4, T4, T3, rT3, TSH and thyroid hormone binding proteins was analysed in 181 of the 460 men, excluding those with past or present goitre, those who were obviously ill or had died between 70 and 75 years of age and those who had any disease or medication influencing free T4 concentrations. Smokers had higher T4 and rT3 levels, and lower TSH levels but T3 levels no different from non‐smokers. The difference in T4 levels, but not rT3 or TSH levels, between smokers and non‐smokers could be attributed to differences in body mass and also to differences in TBG levels. The results indicate that tobacco smoking is associated with long‐term alterations in thyroregulatory function.
TWO TYPES OF THYROID FUNCTION‐BLOCKING ANTIBODIES IN AUTOIMMUNE ATROPHIC THYROIDITIS AND TRANSIENT NEONATAL HYPOTHYROIDISM DUE TO MATERNAL IgG
Authors: TAKASU N. , NAKA M. , MORI T. , YAMADA T.
Published: March 2008

We examined the effects of IgG from four patients with autoimmune atrophic thyroiditis on cAMP responses and iodine metabolism (post‐receptor processes), using cultured thyroid cells. We found two types of thyroid function‐blocking antibodies: (1) one blocks TSH binding to its receptors and inhibits TSH‐stimulated cAMP responses but does not block cAMP‐stimulated iodine uptake and organification; (2) the other blocks TSH binding to its receptors, inhibits TSH‐stimulated cAMP responses and does block cAMP‐stimulated iodine uptake and organification (post‐receptor processes). Among the four patients with autoimmune atrophic thyroiditis, three had TSH binding blocking antibodies only and one had antibodies which block post‐receptor processes. These antibodies might be responsible for thyroid dysfunction in autoimmune atrophic thyroiditis. The daughter of one of the women with autoimmune atrophic thyroiditis had transient neonatal hypothyroidism and recovered spontaneously from the hypothyroid state with the disappearance of the maternal blocking antibodies.
DIFFERENTIAL TSH AND PRL RESPONSES TO DOPAMINE RECEPTOR BLOCKADE IN ACROMEGALY
Authors: PRESCOTT R. W. G. , WEIGHTMAN D. R. , KENDALL‐TAYLOR PAT , JOHNSTON D. G.
Published: March 2008

The serum TSH and prolactin responses to dopamine receptor blockade (domperidone 10 mg i.v.) were measured in eight acromegalic subjects and seven normal controls. The serum TSH response was exaggerated in acromegalics when compared to controls (sum of the increments 12–2 ± 2–8 mU/1 and 40 ± 1 ‐2 mU/1 respectively P & lt; 0–05), whereas the serum prolactin response was blunted (sum of the increments 5029±1377 mU/1 and 14 673 ± 2889 mU/1 respectively P <0–01). Dopamine receptor blockade did not significantly alter basal growth hormone levels in either group. To ascertain whether this response was merely a reflection of high circulating growth hormone levels six normal controls were pretreated for 24 h with either intramuscular growth hormone (three injections of 4 IU) or an equivalent volume of saline before the administration of domperidone (10 mg i.v.). The serum TSH and prolactin responses were not affected by prior growth hormone treatment. The opposite TSH and prolactin responses to dopamine blockade do not allow any firm conclusions to be made about the level of hypothalamic dopamine activity in acromegaly.
THE GENES THAT CONTROL CALCIUM HOMEOSTASIS
Authors: HENDY G.N. , O'RIORDAN J. L. H.
Published: March 2008

Application of the techniques of molecular biology is having a dramatic impact upon endocrinology (for a review, see Hendy & Kronenberg, 1982). This is specifically illustrated here by considering the use of recombinant DNA technology to study some of the main factors that are involved in calcium homeostasis, including parathyroid hormone, calcitonin and vitamin D‐dependent calcium‐binding protein. To varying degrees for these proteins, it has been possible to elucidate the sequence of nucleotides in the appropriate messenger RNA and measure the concentration of specific mRNA in the parathyroid, thyroid or intestine. It has also been possible in some cases to begin to establish the number and the structure of the genes that are involved and to assign a particular gene to a specific chromosome.
ORAL GLUCOSE INHIBITS GROWTH HORMONE SECRETION INDUCED BY HUMAN PANCREATIC GROWTH HORMONE RELEASING FACTOR 1–44 IN NORMAL MAN
Authors: DAVIES R. R. , TURNER S. , JOHNSTON D. G.
Published: March 2008

The interaction between the inhibitory effect on growth hormone secretion of a 75 g oral glucose load and the stimulatory effect of human pancreatic growth hormone releasing factor 1–44 (hpGRF 1–44, 10 μg i.v.) has been studied in six normal subjects. hpGRF 1–44 alone induced a rise in growth hormone concentrations (maximum mean ± SEM, 16–5 ± 1.7 mU/1 15 min after injection) while growth hormone levels were suppressed by oral glucose alone (& < 1 ‐5 mU/1 from 45 to 135 min after glucose ingestion). When hpGRF 1–44 was injected 60 min after oral glucose, the growth hormone response was attenuated (maximum, 6.7±1.4 mU/1 at 15 min, P<005). Increments of blood glucose within the physiological range diminish the growth hormone response to hpGRF 1‐44 in normal man.
PULSATILE SECRETION OF LH IN RELATION TO THE RESUMPTION OF OVARIAN ACTIVITY POST PARTUM
Authors: GLASIER ANNA , McNEILLY A. S. , HOWIE P. W.
Published: March 2008

Changes in the pulsatile pattern of LH secretion in relation to the resumption of ovarian activity post partum have been studied in breast feeding mothers. Basal concentrations of LH were significantly lower than normal both when ovarian activity was completely suppressed and when there was evidence of some follicular development prior to the resumption of menstruation. Once menstruation resumed basal concentrations of LH were unchanged whether ovulation occurred or not. No difference in the frequency or amplitude of pulses in LH secretion could be found at any stage post partum in either breast or bottle feeding women. FSH levels remained constant throughout the post partum period while mean concentrations of prolactin fell as ovarian activity returned to normal. However, during the period of complete suppression of ovarian activity in breast feeding women, two patterns of pulsatile secretion of LH were observed. In 76% of observation periods, basal levels of LH were lower than normal and were characterized by low frequency and low amplitude pulses of LH. In contrast, in the remaining 24% of observation periods, basal levels and pulse amplitude and frequency of LH were similar to those in the follicular phase of normal menstrual cycles in these women. Individual women showed either or both of these patterns of secretion during the period of ovarian suppression post partum. The data suggests that the failure to maintain ovarian follicular development post partum in breast feeding women may be due to: (1) a direct block of LH action at ovarian level, perhaps by the high levels of prolactin associated with lactation and/or (2) an inability of the hypothalamic‐pituitary axis—as a result of the suckling stimulus and/or prolactin—to maintain pulsatile secretion of LH in the face of the negative feedback effects of the increased oestrogen secretion resulting from the initiation of follicular development.
ORAL CONTRACEPTIVE AGENTS DO NOT AFFECT SERUM PROLACTIN IN NORMAL WOMEN
Authors: DAVIS J. R. E. , SELBY C. , JEFFCOATE W. J.
Published: March 2008

A total of 230 healthy women attending family planning clinics took part in a cross‐sectional study, comparing contraceptive histories and serum prolactin levels. It was found that the distribution histogram of serum prolactin was markedly skewed to the right in all main groups, but that the distribution profile was not affected by use of oestrogen‐containing contraceptives. Neither the dose of oestrogens nor duration of their use affected prolactin levels. We have thus found that currently available combined oral contraceptive agents have no effect on serum prolactin. Analysis of the skewed raw data yields a ‘normal’ range of 110‐700 mU/I, higher than that usually accepted.
PITUITARY AND THYROID INSUFFICIENCY IN THALASSAEMIC HAEMOSIDEROSIS
Authors: LIVADAS D. P. , SOFRONIADOU K. , SOUVATZOGLOU A. , BOUKIS M. , SIAFAKA L. , KOUTRAS D. A.
Published: March 2008

Thyroid and pituitary function tests using hypothalamic releasing factors were performed in seven patients with thalassaemia and secondary haemosiderosis and in a control group of seven healthy subjects. The TSH level in the thalassaemic patients (18.07± 1.10 μU/ml) was higher than in the controls (1.01±0.14 μU/ml, P<0.001). After TRH administration the TSH values increased less than in the controls. Serum thyroxine and FT4I values were lower in the group of patients with thalassaemia (76.7 ± 7.8 nmol/1 and 19.3 ± 2.2) compared to the controls (116.1±6.9 nmol/1, P <0.005 and 38.6 ± 3.6, P <0001). The basal prolactin values did not differ significantly between the two groups, but after TRH administration the increment was significantly lower in thalassaemics than in controls (P <0.005). The basal LH values were lower in the thalassaemic patients (1.37±0.24 ng/ml) than in the controls (3.23 ± 0.50 ng/ml) and did not increase significantly after LHRH administration. The FSH values were also lower in the thalassaemic group (0.46±0.15 ng/ml) compared to the controls (2.06±0.08 ng/ml, p <0.001), and increased only slightly after LHRH administration. We conclude that in thalassaemia pituitary deficiency exists, mostly of gonadotrophs, but possibly also for the thyrotrophs and the lactotrophs. Latent primary hypothyroidism has also been found in the thalassaemic group. The functional abnormalities found in both endocrine glands are best explained as a consequence of coexisting haemosiderosis.
A HIGH SENSITIVITY IMMUNOCHEMILUMINOMETRIC ASSAY FOR HUMAN THYROTROPHIN
Authors: WEEKS I. , STURGESS MARIA , SIDDLE K. , JONES M. K. , WOODHEAD J. S.
Published: March 2008

A. two‐site immunochemiluminometric assay (ICMA) has been developed for the measurement of human thyrotrophin (TSH). The procedure involves reaction of serum samples with monoclonal antibodies to TSH which have been labelled with a chemiluminescent acridinium ester followed by reaction with solid‐phase polyclonal antibodies to TSH. The total reaction time is 2 h and bound labelled antibody is quantified luminometrically. The assay has an absolute sensitivity of 0.004 mU/1 and a linear dose‐response range up to 60 mU/1. Circulating TSH concentrations in 84 normal subjects were in the range 0.4 to 4.0 mU/1 and in 16 hyperthyroid patients were less than 0.03 mU/1. This assay should thus prove useful as a first line test of thyroid function.
EFFECT OF METOCLOPRAMIDE ON PLASMA VASOPRESSIN IN MAN
Authors: NOMURA K. , KURIMOTO F. , DEMURA H. , SAKURAI H. , NOMURA T. , ZIBIKI K. , NARUSE M. , KANAI N. , SHIZUME K.
Published: March 2008

The effect of metoclopramide, a dopamine blocker, on arginine vasopressin (AVP) secretion was investigated in normal males. After a bolus injection of metoclopramide (10 mg), all subjects (n= 7) demonstrated an increase of 80‐3% (from 0.71 ±0.12 (Mean ± S.E.) to 1.28 ± 0.24 pg/ml, P± 0005) in plasma AVP at 15 min. In controls (n = 7) plasma AVP levels did not change after saline injection (2 ml). Because plasma osmolality and blood pressure did not change, the elevation of plasma AVP levels induced by treatment with metoclopramide may be due to its central effect as a dopamine inhibitor. Although plasma AVP levels increased again at 90 and 120 min after a bolus injection of metoclopramide, accompanying falls in blood pressure (4‐5%) make the interpretation concerning the contribution of dopamine to AVP secretion in a late phase uncertain. In summary, plasma AVP levels were shown to be significantly increased by a metoclopramide bolus, suggesting that AVP secretion is under tonic inhibition by dopamine.
THE EFFECTS OF BROMOCRIPTINE ON THE SEXUAL BEHAVIOUR OF HYPERPROLACTINAEMIC MAN: A CONTROLLED CASE STUDY
Authors: BANCROFT J. , O'CARROLL R. , MCNEILLY A. , SHAW R. W.
Published: March 2008

A 44‐year old man presented with loss of sexual interest and erectile failure and together with his wife was treated successfully with sexual counselling. He was subsequently found to have been hyperprolactinaemic before and after sex therapy. Comparison of bromocriptine with placebo in two double blind studies showed a modest increase in sexual interest when his prolactin levels fell to normal. In this case, the principal effect of hyperprolactinaemia was on sexual interest. His main problems, erectile impotence and decline in sexual activity, resulted from his and his wife's psychological reaction to this modest hormonal effect. Hyperprolactinaemia appears to have a similar effect to testosterone deficiency in men.
EVIDENCE FOR AN EFFECT OF ANTITHYROID DRUGS ON THE NATURAL HISTORY OF GRAVES' DISEASE
Authors: WEETMAN A. P. , McGREGOR A. M. , HALL R.
Published: March 2008

In the United Kingdom, about half the patients with Graves' disease who are given antithyroid drugs are still in remission one year after treatment is stopped. The most widely held view is that such remission rates are due only to the biochemical effects of the drugs, the disease either spontaneously remitting or abating when the immune system is no longer subject to the stimulatory effects of excessive thyroid hormone. We review here the accumulating evidence against both of these alternatives. In contrast, there is now a large body of work which shows that thyrotrophin receptor antibody levels, central to the aetiology of Graves' hyperthyroidism, fall during antithyroid treatment and that remission may be related to this fall in a fashion which is dependent on the dose and duration of treatment. This immunosuppressive effect is supported by experimental data and on the basis of these results we propose that antithyroid drugs may modify the natural history of Graves' disease and contribute to the remission which occurs in a proportion of treated patients.
POTENTIAL USES OF HUMAN PANCREATIC GROWTH HORMONE‐RELEASING FACTOR 1‐44 AMIDE
Authors: BELCHETZ P. E. , WELDON S. F. , DAVIS J. C. , DIVER M. J. , SMITH C. S. , HARRIS F.
Published: March 2008

A family of growth hormone releasing peptides have been isolated and characterized from human pancreatic islet cell tumours. We have compared the growth hormone release in normal volunteers and patients with various hypothalamo‐pituitary disorders, following direct stimulation of the pituitary using 50μg of the most potent homologue, hp GRF 1‐44 amide i.v. with that following indirect stimulation using oral clonidine 0‐15 mg/m2, which depends on intact hypothalamic mechanisms. These tests both produced a wide variation in GH response in normal volunteers, considerable GH release following hp GRF 1^44 amide but little after clonidine in idiopathic GH deficiency, and indistinguishable, negligible responses in patients with craniopharyngiomas and pituitary tumours associated with GH deficiency. Two untreated acromegalics showed GH increments in the normal range despite elevated basal levels. It is concluded that hp GRF 1‐44 amide is of limited diagnostic value by itself, but may be of considerable therapeutic use in patients with idiopathic GH deficiency.
THYROGLOBULIN SECRETION BY HUMAN THYROID CELLS AFTER MONOLAYER CULTURE–COMPARISON OF NORMAL AND ADENOMATOUS CELLS
Authors: DAVIES T. F. , PLATZER M. , SCHWARTZ A. E. , FRIEDMAN E.
Published: March 2008

We have analysed immunoassayable thyroglobulin (hTg) secretion from both normal and abnormal isolated human thyroid cells after short‐term monolayer culture. All cells were sensitive to more than 10 μU/ml bTSH when assessed by intracellular cyclic AMP accumulation in the presence of a phosphodiesterase inhibitor. hTg release was stimulated in all cells by bTSH in a dose related manner and with a detectable response within 24 h. Basal hTg secretion rates were greater in cells derived from benign follicular adenomata (range 1‐1–2‐2 ng/105 cells/h, n=4) than in normal human thyroid cells (range 0‐1‐0‐65 ng). Therefore it appears likely that hTg secretion by adenomatous thyroid cells was a likely contributor to increased serum hTg in patients with single follicular adenomata. We conclude that simple human thyroid cell monolayers have potential for the further study of hTg secretion and its control by TSH.
RESPONSES TO ANALOGUES OF GROWTH HORMONE‐RELEASING HORMONE IN NORMAL SUBJECTS, AND IN GROWTH‐HORMONE DEFICIENT CHILDREN AND YOUNG ADULTS
Authors: GROSSMAN A. , SAVAGE M. O. , LYTRAS N. , PREECE M. A. , SUEIRAS‐DIAZ J. , COY D. H. , REES LESLEY H. , BESSER G. M.
Published: March 2008

Three analogues of growth hormone‐releasing hormone (GHRH) have been compared in normal subjects. GHRH(1‐29)NH2 is equipotent to GHRH(1‐40); increasing doses from 10‐200 per subject augments the duration of stimulated growth hormone (GH) release, but the peak serum GH shows only a poor correlation with dose. The derivative D‐Ala2‐GHRH(1‐29)NH2 is no more potent than the unsubstituted GHRH(1‐29)NH2. In 20 children and young adults with growth hormone deficiency by conventional criteria, eight showed normal or only slightly subnormal peak serum GH responses to GHRH(1‐40) or GHRH(1‐29)NH2. These included two patients with tumours of the hypothalamus, as well as six with idiopathic isolated growth hormone deficiency or panhypopituitarism. A poor response to GHRH was generally seen in patients on long‐term GH therapy. Priming with GHRH, in either a single bolus or a continuous infusion, did not increase the GH response to GHRH. It is concluded that GHRH(1‐29)NH2 is a useful analogue in the testing of GH reserve in patients with growth hormone deficiency, and has considerable potential for long‐term therapy.
INHIBITION OF PHYSIOLOGICAL GROWTH HORMONE SECRETION BY ATROPINE
Authors: TAYLOR B. J. , SMITH P. J. , BROOK C. G. D.
Published: March 2008

We have investigated the effects of atropine (specific muscarinic cholinergic inhibition) on the nocturnal secretion of GH during the first cycle of stage IV sleep in six normal volunteers and three tall adolescents. Atropine was administered orally in a dose of 0·6 mg (n= 8) or 1·8 mg (n= 4) 30 min before expected sleep and the sampling repeated. Peak GH level without atropine was 45·3 mU/l (range 5·7 to 92·0): both doses of atropine abolished sleep associated GH secretion. Spontaneous daytime GH secretion was demonstrated during five 6 h sampling periods in three normal adults. There was a significant decrease in spontaneous daytime GH secretion when the sampling was repeated after atropine 0·6 mg or 1·8 mg. We conclude that inhibition of GH secretion using anticholinergic drugs should be further investigated in the management of excessive growth hormone secretion.
NALOXONE REDUCES THE FENFLURAMINE‐INDUCED PROLACTIN RELEASE IN MAN
Authors: FORESTA C. , SCANELLI G. , INDINO M. , FEDERSPIL G. , SCANDELLARI C.
Published: March 2008

In order to ascertain whether there is a relation between opioids and the serotoninergic system in prolactin (PRL) secretion increase, we investigated in seven healthy men (21 to 26 years of age) the effect of naloxone, a specific opioid antagonist, on PRL secretion induced by fenfluramine, a drug that stimulates serotonin release and inhibits its re‐uptake. We observed that subjects receiving fenfluramine (60 mg orally) had a significantly (P < 0·001) higher increase in PRL plasma levels than the controls receiving placebo. In all subjects naloxone infusion at a dose of 15 mg caused a significant reduction (P < 0·0005) in the PRL response to fenfluramine. Higher doses of naloxone (30 mg) do not further inhibit the PRL secretion induced by fenfluramine. These results suggest that naloxone may interact with opiate receptors on serotonin neurons thereby reducing the synthesis and release of serotonin. It seems that in man, therefore, there is an interplay between opiates and the serotoninergic system in the facilitatory influence on PRL release.
TESTOSTERONE REPLACEMENT IN HYPOGONADAL MEN: EFFECTS ON OBSTRUCTIVE SLEEP APNOEA, RESPIRATORY DRIVES, AND SLEEP
Authors: MATSUMOTO A. M. , SANDBLOM R. E. , SCHOENE R. B. , LEE KATHRYN A. , GIBLIN ELIZABETH C. , PIERSON D. J. , BREMNER W. J.
Published: March 2008

The obstructive sleep apnoea syndrome occurs predominantly in men. To determine the effect of testosterone on ventilatory function and whether testosterone may play a role in the development of obstructive apnoea, we performed waking ventilatory drive studies and sleep studies in five hypogonadal men. These androgen‐deficient subjects were studied both while receiving no treatment and after six weeks of testosterone replacement therapy (testosterone oenanthate 200 mg i.m. every 2 weeks). Hypoxic ventilatory drive decreased significantly, from 158 · 39 (mean · SEM) off testosterone to 88 · 19 on testosterone therapy (P < 0.05). Hypercapnoeic ventilatory drive did not change significantly on testosterone. Obstructive sleep apnoea developed in one man and markedly worsened in another man in association with testosterone administration. Both of these subjects also exhibited marked decreases in oxygen saturation with the development of cardiac dysrhythmias during sleep and large increases in haematocrit. The remaining three hypogonadal men did not demonstrate significant sleep apnoea either on or off testosterone. The percentage of sleep time spent in REM sleep increased from 14 · 3% to 22 · 2% when the men were receiving testosterone (P < 0.01), but the episodes of sleep apnoea tended to occur during non‐REM sleep. We conclude that in some hypogonadal men, replacement dosages of testosterone may affect ventilatory drives and induce or worsen obstructive sleep apnoea. The obstructive sleep apnoea syndrome is a potential complication of testosterone therapy. These results suggest that androgen levels present in normal man may play an important role in the pathogenesis of obstructive sleep apnoea.
MAGNESIUM ADMINISTRATION REVERSES THE HYPOCALCAEMIA SECONDARY TO HYPOMAGNESAEMIA DESPITE LOW CIRCULATING LEVELS OF 25‐HYDROXYVITAMIN D AND 1,25‐DIHYDROXY VITAMIN D
Authors: FUSS M. , COGAN E. , GILLET C. , KARMALI R. , GEURTS J. , BERGANS A. , BRAUMAN H. , BOUILLON R. , CORVILAIN J.
Published: March 2008

The effect of parenteral administration of magnesium was studied in five patients with hypomagnesaemic hypocalcaemia. The initial metabolic state was characterized by a normal level of serum immunoreactive parathyroid hormone (iPTH), and by low or undetectable serum 25‐hydroxyvitamin D (25OHD) and 1,25‐dihydroxyvitamin D (1,25 (OH)2D). A parathyroid response was elicited by the acute intravenous injection of magnesium chloride. In contrast, 1,25(OH)2D did not change up to 24 h after the injection. Intramuscular magnesium sulphate restored serum magnesium and calcium to normal, whereas iPTH was transiently increased. 25OHD remained low and unchanged. 1,25(OH)2D rose very slowly, but the correction of hypocalcemia began before any change in 1,25(OH)2D levels could be demonstrated. Thus, the early correction of hypocalcemia mainly depended on the restoration of an adequate parathyroid function independently of the secretion of 1,25(OH)2D.
RELATIONSHIP BETWEEN SERUM THYROGLOBULIN AND INTRATHYROIDAL STABLE IODINE IN HUMAN SIMPLE GOITRE
Authors: UNGER J. , DE MAERTELAER V. , GOLSTEIN J. , DECOSTER C. , JONCKHEER M. H.
Published: March 2008

Serum thyroglobulin levels are increased in many patients with simple goitre. This increase has been attributed to the release of thyroglobulin (Tg) from the colloid of necrosed follicles. To test the hypothesis that increased serum Tg could be related to the low intrathyroidal iodine concentration [I], the main cause of nontoxic goitre, these two variables were measured in 91 euthyroid goitrous patients and compared to serum free T3 and free T4 levels as well as thyroid weight. Thyroid iodine concentration was estimated from the X‐ray fluorescence measurement of intrathyroidal iodine stores and from the weight of the gland estimated by planimetry. Serum Tg levels, the free T3/T4 ratio and thyroid weight were negatively correlated to [I] (Spearman's coefficient of correlation=−0.44(P= 0.001); −0.30(P= 0.006); −0.33(P= 0.001), respectively). Tg levels were also positively correlated to the T3/T4 ratio (R= 0.28, P= 0.008) and to the weight of the gland (R= 0.37; P= 0.001). These data suggest that, in simple goitre, increased serum Tg concentrations are partly related to the reduced concentration of iodine in goitre tissue (as are an increased T3/T4 ratio and the size of the goitre) and is not only the reflection of follicular necrosis.
URINARY STEROID METABOLITES IN SUBJECTS WITH MALE PSEUDOHERMAPHRODITISM DUE TO 5α‐REDUCTASE DEFICIENCY
Authors: PETERSON R. E. , IMPERATO‐McGINLEY JULIANNE , GAUTIER T. , SHACKLETON C.
Published: March 2008

To investigate the enzymatic basis for abnormal steroid metabolism in subjects with male pseudohermaphroditism due to 5α‐reductase deficiency, the ring A reduced urinary 5β and 5α metabolites of testosterone, androstenedione, 11β‐hydroxyandrostenedione, cortisol and corticosterone were measured by gas chromatography. Assays of the four pairs of urinary 5β and 5α steroid metabolites revealed decreased conversion of the parent steroids to 5α‐reduced urinary metabolites, with increased 5β to 5α urinary steroid metabolite ratios. These studies establish that increased urinary 5β/5α ratios are distinctive for this disorder, and represent the most reliable method for confirming the diagnosis of primary inherited 5α‐reductase deficiency. These data also suggest that the conversion on the many Δ4‐3 ketosteroids to 5α‐reduced steroids may be due to a single enzyme with broad specificity, or multiple enzyme reductases with a common regulator.