bluuebunny/crossref_metadata_2025 huggingface dataset:
Control of testicular steroidogenesis in foetal rat: effect of decapitation on testosterone and plasma luteinizing hormone-like activity
Authors: Habert R. , Picon R.
Published: December 2008

These studies were designed to investigate the regulation of testicular testosterone and the role of the hypophysis during the last 5 days of gestation in the rat. Plasma LH-like activity was measured by bioassay and testosterone by radioimmunoassay. In both sexes, plasma LH-like activity levels were low on days 17.5 and 18.5 (< 0.10–0.26 ng/ml) and rose on day 19.5 (0.10–1.25 ng/ml). Thereafter the levels increased considerably and were significantly higher in females than in males: on day 21.5 they reached 0.44–2.42 ng/ml in males and 2.20–3.96 ng/ml in females. Plasma levels of testosterone were significantly higher in males than in females and were maximal on day 18.5 in males. Testicular content of testosterone reached maximum values on day 18.5 and remained constant thereafter. Foetal decapitation clearly reduced testicular production of testosterone and plasma LH-like activity only after day 19.5. A residual gonadotrophic activity was detected at all stages in decapitated foetuses from both sexes (< 0.10–0.46 ng/ml). These results suggest that pituitary LH secretion and pituitary-testicular interrelationships are essentially established between day 19.5 and 20.5, and that the ageing testis becomes more dependent on gonadotrophic stimulation. The existence of an extrapituitary LH-like activity might indicate the presence of placental gonadotrophins.
Serum levels of prolactin, TSH and gonadotrophins following LRH/TRH - double stimulation tests during the menstrual cycle
Authors: Baumgarten S. , Römmler A. , Post K.G. , Hammerstein J.
Published: December 2008

The objective of this study was to re-investigate the capacity of pituitary prolactin (Prl) and thyrotrophin (TSH) secretion throughout the normal menstrual cycle to respond to repeated thyrotrophin releasing hormone (TRH) stimulation analogous to the double luteinizing hormone-releasing hormone (LRH) stimulation test. This test has been shown to be a sensitive parameter for oestrogenic effects on the gonadotrophs. In addition, the volunteers were selected carefully on the basis of ovulatory cycles and otherwise normal endocrine function.

In 9 women a combined LRH/TRH double stimulation test was performed during the early follicular, periovulatory and mid-luteal phases. TRH (200 μg) and LRH (25 μg) each were given iv twice, 2 h apart.

Basal and LRH stimulated luteinizing hormone (LH) and follicle stimulating hormone (FSH) were found to follow characteristic cyclic response patterns. The LH responses after both LRH stimulations were greatest in the periovulatory phase; Δ1 and Δ2 were higher in the mid-luteal phase than in the follicular phase. Maximum FSH response to LRH was found during the periovulatory phase, but the FSH response in the early follicular phase was greater than that found in the mid-luteal phase. In contrast, basal and TRH stimulated serum concentrations of TSH and Prl remained constant throughout the cycle.

The gonadotrophin ratios Δ2:Δ1 were generally greater than 1. They increased from 1.4 in the early follicular phase to 3.0 in the late follicular phase, concomitant with the rise in oestrogens. The Δ2: Δ1 ratios for TSH and Prl were less than 1, ranging from 0.66 to 0.98 for TSH and from 0.26 to 0.99 for Prl. They did not show any cyclic changes.

Thus, this study shows that after LRH/TRH double stimulation, the gonadotrophin but not the Prl and TSH responses vary with the physiological changes in oestrogens during the menstrual cycle.

The supposed mechanism of oestrogen effects on pituitary hormone secretion and their possible clinical significance are discussed.
Glycoprotein hormone α-subunit secretion in patients with pituitary adenomas: influence of TRH, LRH and bromocriptine
Authors: MacFarlane I. A. , Beardwell C. G. , Shalet S. M. , Ainslie Gill , Rankin Elaine
Published: December 2008

Twelve patients with pituitary adenomas and increased serum concentration of the glycoprotein hormone α-subunit were studied. Eight patients were acromegalic and one had a FSH1 producing tumour. The adenomas in 9 patients had undergone subtotal operative removal and/or external irradiation but no patient was studied within 3 months of these treatments.

Many of the acromegalic patients, with moderately elevated α-levels, showed marked increases in α-concentration after TRH and/or LRH, compared with controls. The non-acromegalic patients, with the highest α-levels, showed poor responses to releasing hormones. These results suggest that excessive α-subunit secretion in acromegalic patients is often under hypothalamic control whereas in non-acromegalic patients it is often autonomous.

Seven patients, 4 with acromegaly, were then given oral bromocriptine, 5 mg over 3 h. There was a significant fall in log mean α-level at 4 and 5 h (P < 0.02). Six patients took bromocriptine for 1–2 months. Log mean α-concentration was significantly reduced at the end of treatment (P < 0.02) and then recovered to basal levels after stopping treatment for one week. α-Subunit hypersecretion in some patients with pituitary adenomas is therefore modulated by dopaminergic control mechanisms.
Properties of thyrotrophin receptors in human thyroid membranes
Authors: de Bruin Tjerk W. A. , van der Heide Daan
Published: December 2008

The influence of pH, salts, temperature and time of incubation on the binding of [125I]thyrotrophin to its human thyroid receptor was studied. Optimal binding was achieved at pH 7.0–7.6. Pre-incubation of membrane receptors at pH 6.0 resulted in a 60% loss of binding. There was dynamic equilibrium, as demonstrated by kinetic experiments. Scatchard analysis yielded non-linear plots with apparent affinity constants of 1.9 × 109 m−1 and 3.7 × 107 m−1. The concentration of [125I]thyrotrophin used in the experiments (1.2–2.2 pm) approximated normal human serum thyrotrophin concentration.
Refractoriness of TSH- and PGE2-stimulated iodine metabolism in cultured porcine thyroid cells, evidence for refractoriness at the level of cAMP action
Authors: Takasu Nobuyuki , Sato Akira , Yamada Takashi , Shimizu Yoshifusa
Published: December 2008

In an attempt to study intrinsic regulatory mechanism involved in iodine metabolism, chronic and acute effects of TSH, PGE2 and DBC on iodine uptake, iodide discharge and organic binding of iodine were examined using cultured porcine thyroid cells.

Culture in the presence of TSH, PGE2 and DBC for 6 days maintained the ability of thyroid cells to take up iodide and organify it, but culture in the absence of these substances failed to do so. When incubated with Nal in the presence of 1 mm methylmercaptoimidazole (MMI), the cells took up iodide and this accumulated iodide was discharged by TSH, PGE2 and DBC. TSH-, PGE2- and DBC-stimulated iodide discharge was depressed greatly after chronic exposure to TSH, PGE2 or DBC. This refractoriness of TSH-, PGE2- or DBC-stimulated iodide dishcarge was not specific for each thyroid stimulating substance; previous exposure to TSH, PGE2 or DBC induced refractoriness of TSH-, PGE2- and DBC-stimulated iodide discharge, providing evidence for the existence of refractoriness at the level of cyclic AMP action on iodide discharge. When incubated with Nal in the absence of MMI, the cells took up iodide and organified it. After 30 min incubation with Nal, TSH, PGE2 and DBC were added and they stimulated iodide organification further. This TSH-, and PGE2-stimulated iodide organification was also depressed after exposure to TSH or PGE2.

These data indicate that, as an intrinsic regulatory mechanism, refractoriness is operating at the level of cAMP action on iodine discharge and organification.
Maturation of renal and hepatic monodeiodination of thyroxine to triiodothyronine and post-natal changes of serum thyroid hormones in young rats
Authors: Suzuki Yukichi , Kita Kyoko , Uchigata Yasuko , Takata Ikuro , Sato Tamotu
Published: December 2008

Maturational changes of renal and hepatic 5′-monodeiodination of thyroxine (T4) and post-natal changes of serum thyroid hormone levels were investigated in young rats under 35 days of age. Renal T3 generation in the 1-day-old rats was low, rose progressively to a level of more than 200% of the adult rats on days 21 and 28 and declined thereafter. In contrast, hepatic T3 generation increased from an initial low activity to a plateau after 7 days of age, which was 1½ times higher than that of adult rats. Because of the extremely low value of serum T4 in the neonatal period, T3/T4 and rT3/T4 ratios were elevated on day 7. The ratio of rT3/T4 decreased gradually and became stable after 21 days of age, while the T3/T4 ratio increased reciprocally to a peak on days 21 and 28, corresponding to the period of maximal activity of renal T4 monodeiodination. These results indicate that in addition to elevated hepatic T4 monodeiodination, renal conversion of T4 to T3 may play a significant physiological role during the period of enhanced T3 requirement for maturation.
Treatment with cimetidine in patients with primary hyperparathyroidism
Authors: Ljunghall Sverker , Åkerström Göran , Rudberg Claes , Selking Orjan , Johansson Henry , Wide Leif
Published: December 2008

Treatment with cimetidine (1000 mg daily in four divided doses) was given for 3–20 weeks to 10 patients with primary hyperparathyoidism (HPT). All patients had hypercalcaemia and raised serum concentrations of parathyroid hormone (PTH). During treatment no consistent effects were noted on either serum calcium or PTH and normalization did not occur in any case. Hypergastrinaemia was demonstrated in 6 patients and was also unaffected by therapy while in the 4 patients with normal pre-treatment gastrin values a slight increase was seen.

This study does not support the view that cimetidine can be of use for the treatment of primary HPT.
Acetate: inhibitor of growth hormone hypersecretion in diabetic and non-diabetic uraemic subjects
Authors: Ørskov Hans , Hansen Aage Prange , Hansen Hans Erik , Alberti K. George M. M. , Noy George A. , Nosadini Romano
Published: December 2008

Five diabetic and 14 non-diabetic uraemic patients on long-term haemodialysis were studied during twenty-one 24 h periods including 5 to 7 h of haemodialysis against glucose-free acetate buffered dialysis fluid. Half-hourly blood samples were collected for hormonal and metabolite analysis. In addition, blood samples were analyzed in 40 experiments covering the haemodialysis and a pre-dialysis period. Before dialysis, plasma growth hormone levels were high and fluctuating, but almost always fell to low normal values within the first 2 h of haemodialysis.

In the diabetic uraemic patients, the occasional severe hypoglycaemic episodes occurring during haemodialysis did not provoke growth hormone release, and hypoglycaemic reactions were not encountered.

Intravenous acetate infusion studies resulted in plasma concentrations ranging from 1.3 to 2.7 mmol, i.e. about 60 per cent of the levels reached during haemodialysis and in suppression of growth hormone secretion. It is suggested that the fall in growth hormone levels and the lack of hypoglycaemic symptoms during haemodialysis is due to the use of acetate as a fuel in brain.
Isolated ACTH deficiency and primary hypothyroidism
Authors: Miller Michael J. , Horst Tomm Vander
Published: December 2008

A patient presented with severe primary hypothyroidism and secondary adrenal insufficiency due to the isolated deficiency of ACTH. The diagnostic evidence suggests that both are of an autoimmune aetiology. Acquired isolated or unitrophic ACTH deficiency is a rare but definite cause of adrenal insufficiency. Additional case reports and autopsy studies describing acquired isolated ACTH deficiency associated with autoimmune thyroid disease have appeared in the literature suggesting that the association is more than coincidental. Combined thyroid and adrenal failure should not always be considered to be the result of combined end organ failure. Unitrophic isolated ACTH deficiency may co-exist with primary hypothyroidism.
Plasma noradrenaline and adrenaline in pre-eclampsia, essential hypertension in pregnancy and normotensive pregnant control subjects
Authors: Pedersen E. B. , Rasmussen A. B. , Christensen N.J. , Johannesen P. , Lauritsen J. G. , Kristensen S. , Wohlert M.
Published: December 2008

Noradrenaline and adrenaline in plasma were determined in 15 patients with pre-eclampsia, 10 pregnant patients with essential hypertension, 2 patients with transient hypertension in pregnancy, 11 normotensive pregnant control subjects, and 16 non-pregnant normotensive control subjects. Measurements were performed in the second and third trimester, 5 days, and 3 months after delivery. Comparison within groups showed no significant differences in plasma noradrenaline or adrenaline between levels in pregnancy, 5 days after delivery, and 3 months after delivery in neither pre-eclampsia, essential hypertension nor normotensive pregnant control subjects. Comparison between groups showed no significant differences between the levels in pre-eclampsia, essential hypertension and normotensive pregnant control subjects, neither in pregnancy nor after delivery. Plasma noradrenaline and adrenaline in pregnancy were the same as in normotensive non-pregnant control subjects. Plasma noradrenaline and blood pressure were not correlated in any of the groups. It is concluded that the sympathetic adrenergic activity evaluated by plasma catecholamines is normal in patients with pre-eclampsia and pregnant patients with essential hypertension.
The concentration of progesterone, 20α-dihydroprogesterone, testosterone, oestrone and oestradiol-17β in serum, amniotic fluid and placental tissue of pregnant rabbits
Authors: Lau I. F. , Saksena S. K. , Salmonsen R.
Published: December 2008

The concentrations of progesterone (Δ4P), 20α-dihydroprogesterone (20α-DHP), testosterone (T), oestrone (E1) and oestradiol-17β (E2β) in peripheral blood serum (PBS), amniotic fluid (AF) and placental tissue of rabbits during gestation were determined by radioimmunoassay. The placenta of the 10-day pregnant rabbit was fragile and composed mainly of maternal tissue. By the 12th day of pregnancy it was separable into maternal and foetal placentae. The mean concentration of Δ4P in PBS rose from 200 pg/ml (day 1 of pregnancy) to 17–21 ng/ml (days 10–15) and decreased gradually to 1 ng/ml a few hours before parturition. The 20α-DHP in PBS also showed an increase from 1.5 ng/ml (day 1) to 12 ng/ml (day 6) but fluctuated thereafter. The concentration of 20α-DHP in the PBS tended to be lower than that of Δ4P during pregnancy until the regression of the corpus luteum. An interesting observation was an increase of T on days 6–8 of pregnancy, the time when implantation occurs. The concentrations of E1 and E2β in PBS remained very low throughout pregnancy. Δ4P and 20α-DHP in AF ranged between 25 pg to 1 ng/ml and in no case during the course of pregnancy were the levels of T, E1 and E2β in AF higher than in PBS. Where the maternal placental Δ4P content remained between 1–2 ng/placenta, the foetal placenta Δ4P rose to a level of 15 ng/placenta by day 31 of pregnancy. A similar trend was recorded for 20α-DHP content. It is concluded that although a parallelism between PBS and myometrial steroid concentration was observed, no relationship could be drawn between the concentrations of steroid in PBS and those of the placental tissue and AF.
Steroid metabolism by a tumour of the specific gonadal stroma in a child
Authors: de Niepomniszcze Alicia Barmach , Rivarola Marco A. , Chemes Héctor E. , Bergadá César
Published: December 2008

A study of steroid metabolism by a tumour of the specific gonadal stroma was carried out in a 10 year old boy. Tumours developed in the two testes from multiple foci, and clinically, no signs of sexual development were evident. Four testicular enzymes necessary for testosterone biosynthesis were estimated in the child, in two adult controls, and in three pre-pubertal boys with male pseudohermaphroditism but normal tests of Leydig cell function. 17α-Hydroxylase and 17β-hydroxysteroid dehydrogenase were similar in the five controls and in the gonad with the tumour, while 17,20-desmolase and 3β-hydroxysteroid dehydrogenase were grossly deficient in the child with the tumour. These enzyme deficiencies might explain the absence of peripheral virilization in a boy with a tumour of Leydig and Sertoli cells.
Vast release of submaxillary mouse renin to saliva after stimulation with cholinergic, β-adrenergic but especially α-adrenergic agonists
Authors: Pedersen Erik Bækkelund , Poulsen Knud
Published: December 2008

α-adrenergic stimulation with phenylephrine causes release of vast amounts of mouse submaxillary gland renin to saliva. The amount released is about 100-fold higher than that released after β-adrenergic stimulation with isoproterenol and about 1000-fold higher than the amount released after cholinergic stimulation with pilocarpine. α-blockade with phenoxybenzamine before phenylephrine stimulation strongly inhibits the renin release. However, phenoxybenzamine or β-blockade with propranolol before isoproterenol stimulation have no effect on the amount of renin released. Thus, the release of submaxillary mouse renin to saliva is triggered mainly by activation of α-adrenergic receptors. Renin in cholinergic and α- and β-adrenergic stimulated saliva has the same molecular weight and the same specific enzymatic activity as renin in the submaxillary gland. This indicates that renin is secreted to saliva, and probably also to the blood, in its fully enzymically active 40 000 mol. wt. form regardless of the stimulus used.

The vast amounts of renin released to saliva (up to 600 Goldblatt Units) demonstrate that submaxillary mouse renin is secreted predominantly to saliva and much less to the blood. The mouse submaxillary gland therefore seems to have an exocrine rather than an endocrine role for release of renin.
Effect of bromocriptine and metergoline in the treatment of hyperprolactinaemic states
Authors: Ambrosi Bruno , Travaglini Pietro , Moriondo Paola , Nissim Marina , Nava Claudio , Bochicchio Domenico , Faglia Giovanni
Published: December 2008

The effects of bromocriptine or metergoline treatment were evaluated in 80 hyperprolactinaemic patients (62 women and 18 men). The patients were subdivided into 4 groups: group A) 16 women with idiopathic hyperprolactinaemia; group B) 19 women with untreated Prl-secreting microadenomas; group C) 27 women with unsuccessfully operated prolactinomas; group D) 18 men with unsuccessfully treated macroprolactinomas. Sixty-eight patients were given bromocriptine (2.5–20 mg/day) for 3–58 months and 33 patients were given metergoline (4–16 mg/day) for 3–19 months. Bromocriptine and metergoline were equally effective in the treatment of functional hyperprolactinaemia and of untreated microadenomas, while bromocriptine showed a more potent Prl-lowering effect than metergoline in patients with higher Prl levels and large prolactinomas; both drugs restored the gonadal function to a similar extent, though metergoline was effective in some cases, even in the absence of full Prl suppression. Bromocriptine seems to exert an antitumoral effect, as documented by CT scan in some patients with macroadenomas, but the precise role of both drugs with respect to dose, length of treatment and effectiveness after withdrawal needs to be evaluated further.
Circadian rhythm of mitotic activity in normal and hyperplastic rat thyroid
Authors: Wynford-Thomas D. , Stringer B. M. J. , Williams E. D.
Published: December 2008

This study was designed to provide a reliable quantitative assessment of the circadian rhythm of mitotic activity in the follicular cell population of the rat thyroid, and the effect on this rhythm of prolonged stimulation by a raised level of circulating TSH, induced by goitrogen administration.

Mitotic activity in groups of control and goitrogen-treated rats was assessed by a stathmokinetic technique during four 4-h periods spaced equally through one 24-h cycle. Particular attention was paid to the method of sampling to eliminate systematic and minimise random errors, and to the assesment of rhythmicity which was carried out by an appropriate statistical method.

A highly significant circadian rhythm was found in control animals with a daytime peak (12.00 to 16.00 h). Goitrogen treatment led to a 5- to 6-fold increase in the mean but a loss of detectable rhythmicity.

The results show that the presence and timing of this circadian rhythm must be taken into account in future studies of thyroid growth, and they throw some light on the possible mechanisms of its control. Comparison of the rhythm with that of serum TSH reported previously raises the possibility of a dominant control by this hormone even in euthyroid animals and suggests that it may act on cells in the G2 and/or G1/G0 phases of the cell cycle.
Effects of dexamethasone on the hypothalamic-pituitary-thyroid axis in rats
Authors: Mitsuma Terunori , Nogimori Tsuyoshi
Published: December 2008

Effects of dexamethasone on the hypothalamic-pituitary-thyroid axis in rats were studied. Rats given saline (group A), 25 μg of dexamethasone/100 g body weight (group B) or 500 μg of dexamethasone/100 g body weight (group C) were serially decapitated and brain tissues and blood were obtained. TRH contents in the hypothalamus, plasma concentrations of TRH, TSH, T4, T3 and reverse T3 were measured by specific radioimmunoassay. TRH contents in the hypothalamus were significantly increased at 3 h in group B after dexamethasone treatment. In group C, however, they significantly increased for 1 to 3 h, but then decreased with the minimum at 20 h. TRH plasma levels significantly increased with the maximum at 4 h in group B and at 24 h in group C. TSH plasma levels were significantly decreased initially and then significantly increased with the maximum at 5 h in group B and at 24 h in group C. TSH responsiveness to TRH was significantly decreased at 1 to 3 h in group B, but in group C it was significantly decreased initially and then significantly increased. T3 plasma levels significantly decreased at 1 to 3 h in group B and at 1 to 18 h in group C. Reverse T3 plasma levels were significantly increased with the maximum at 3 h in group B and at 6 h in group C.

The results demonstrate that dexamethasone may act on multiple sites of the hypothalamic-pituitary-thyroid axis in rats and that its effect depends on the dose used or the time interval after dexamethasone treatment.
Radioimmunoassay for 13, 14-dihydro-15-ketoprostaglandin F2α and its application in normo- and anovulatory women
Authors: Schlegel Werner , Urdinola Jaime , Schneider Hermann P. G.
Published: December 2008

Highly specific antibodies to 13, 14-dihydro-15-ketoprostaglandin F2α (PGFM) were raised in rabbits. The animals were immunized with PGFM-bovine serum albumin (BSA)-conjugates.

Prior to the incubation procedure PGFM was extracted by a rapid method with dichloromethane followed by column chromatography.

The antisera dilution was 1:10000 and the cross-reactivity towards prostaglandin A2, E2, F2α, 13, 14-dihydro-15-ketoprostaglandin E2 and the 15-ketoprostaglandin E2 and F2α was < 1%. The limit of detection was 1.9 ± 0.6 pg/ml plasma over the standard range 1.9–250 pg. The intra- and inter-assay variations were 3.9 and 15%, respectively.

PGFM was measured throughout the menstrual cycle in female volunteers.

In normal ovulatory women (n = 3) plasma levels of PGFM varied between 65.6 to 107.1 pg/ml.

No significant variations of plasma PGFM were seen during the cycle. In anovulatory women (n = 4) no difference of PGFM was found during the cycle. PGFM levels in hyperprolactinaemic but ovulating women tend to be higher than in anovulatory, and normoprolactinaemic subjects.

These data strongly indicate that PGFM is not correlated with other hormonal parameters tested here in the normal and anovulatory cycles.
The 'boar taint' steroid 5α-androst-16-en-3-one: an immunisation trial
Authors: Shenoy E. V. B. , Daniel M. J. , Box P. G.
Published: December 2008

Entire and castrated male pigs were actively immunised against the steroid 5α-androst-16-en-3-one (androstenone) conjugated to bovine thyroglobulin as its carrier protein. This immunogen was incorporated with either Freund's complete adjuvant or a water-in-oil emulsion adjuvant; only the latter was found to be acceptable in the pig tissue.

Levels of free and antibody-bound androstenone were measured in the plasma of immunised and control boars. In the controls, levels of free androstenone rose from 15 ng/ml at 13 weeks old to 36 ng/ml at 27 weeks. In the immunised boars, levels of free steroid fell from 16 ng/ml at 13 weeks old to zero at 17 weeks old while levels of antibody-bound androstenone rose from zero at 13 weeks old to a mean level of 70 ng/ml at 27 weeks.

When immunised and control boars and non-immunised gilts were killed at 135 kg live weight, the levels of androstenone in their carcass fat were measured. Their meat was also subjected to organoleptic testing at the Meat Research Institute, Langford. Meat from animals whose fat contained significant levels of androstenone (0.4–1.6 μg/g) was found to taste of 'boar taint' while meat from control gilts with low fat levels of the steroid (0.1–0.2 μg/g) tasted normal.

The uptake of [3H]androstenone was compared in 12 separate body tissues of one immunised and one control boar. No significant differences were found. The presence of specific antibody in the immunised boar had not inhibited movement of steroid between plasma and body tissue.

Some hypotheses raised by these findings are discussed and the likelihood of successfully using immunisation against 'boar taint' is examined and questioned.
Further evidence for calcitonin gene duplication: the identification of two different calcitonins in a fish, a reptile and two mammals
Authors: Cano R. Perez , Girgis S. I. , Maclntyre I.
Published: December 2008

In order to investigate the possibility of the simultaneous expression of two different calcitonin genes during evolution, we studied the nature of calcitonin in: eel pericardium, salamander branchial region, rat thyroid, ox thyroid, medullary carcinoma of the human thyroid and human thyrotoxic goitre.

Sensitive and specific RIAs for human calcitonin (hCT) and salmon calcitonin (sCT) were used in combination with high pressure liquid chromatography (HPLC).

We found that two different immunoreactive calcitonins resembling hCT and sCT exist in eels, salamanders and rats. The major form is i-sCT-like in eels and salamanders, while it is i-hCT-like in rats. Extracts of ox thyroid contained, in addition to the major artiodactyl-CT, an i-hCT-like material. The various human thyroid extracts studied, contained i-hCT but no i-sCT-like material.

This study demonstrates the simultaneous expression of two different calcitonin genes in several species. Taken with the presence of molecules resembling sCT and hCT in birds, this further evidence is consistent with duplication of the calcitonin gene early in vertebrate evolution.
Restoration of the LH surge and ovulation by insulin in alloxan-diabetic immature rats treated with pregnant mare's serum gonadotrophin
Authors: Kirchick Howard J. , Keyes P. Landis , Frye Billy E.
Published: December 2008

Immature alloxan-diabetic rats injected with pregnant mare's serum gonadotrophin (PMSG) do not ovulate and the LH surge is absent. In the present studies we have examined the effects of several insulin treatments on the LH surge and ovulation in alloxan-diabetic rats. Rats were made diabetic by injection of alloxan on day 24 of age. Only those rats with fasting blood glucose concentrations exceeding 180 mg/100 ml on day 27 were considered diabetic. PMSG was injected on day 30. Rats received insulin either by injection (2, 3, 4 or 6 IU/100 g/day; Ultralente B.I.D.) or by subcutaneous implants (Alzet osmotic minipumps; 1.8 or 2.4 IU/day). None of the diabetic rats without insulin treatment ovulated. Some of the animals in each insulin treatment group ovulated, however, the percentage of animals ovulating was highly variable from experiment to experiment when the insulin was given by injection. When insulin was administered by osmotic minipump, the results were more consistent, with at least 60% of the rats ovulating in each experiment. LH surges were found on the afternoon of presumed pro-oestrus (day 32) in diabetic insulin-treated rats which ovulated. In confirmation of previous results, rats without insulin treatment did not have LH surges. Although the site of insulin action has not been determined, these data indicate that the LH surge mechanism in the immature PMSG-treated rat is insulin-dependent.
Simultaneous perfusion of [4-14C]oestriol and [6,9-3H2]oestriol 16α-monoglucuronide through the isolated rat liver
Authors: Höller M. , Weber H. , Breuer H.
Published: December 2008

The uptake of [4-14C]oestriol by the isolated perfused rat liver is 3.8 times faster as compared to that of simultaneously perfused [6,9-3H2]oestriol 16α-monoglucuronide. During perfusion the concentration of both radioactive oestrogens decreased exponentially in perfusion medium (apparent kel: 0.061 min−1 and 0.016 min−1, respectively). [6,9−3H2]Oestriol 16α-monoglucuronide was metabolized only to a small extent; more than 92% was secreted unchanged into the bile where it was highly concentrated (1800 nmol/g). In contrast [4-14C]oestriol was extensively metabolized; it was mainly hydroxylated at C-atom 2, leading to a rapid increase in the concentration of 2-hydroxyoestriol in the perfused medium. This metabolite was quickly taken up by the liver during recirculation and subsequently either methylated or sulphated. 2-Hydroxyoestriol monosulphate was glucuronated to 2-hydroxyoestriol 16α-monoglucuronide 3-sulphate, which was rapidly excreted into the bile. No double conjugate was formed when [6,9-3H2]oestriol 16α-monoglucuronide was perfused; this is additional evidence for the correctness of the assumption that monoglucuronides cannot serve as precursors of sulphoglucuronides.
Ovulation in the rabbit following intraventricular and intravenous administration of synthetic Gn-RH
Authors: Bruni J. E. , Montemurro D. G. , Clattenburg R. E.
Published: December 2008

A comparison was made of the efficacy of intravenously (iv) and intraventricularly administered synthetic Gn-RH in inducing ovulation in conscious and urethane anaesthetized rabbits. Via the iv route of administration, the minimum dose of Gn-RH required to induce ovulation in all animals of the conscious group was 300 ng/kg body weight. This is in contrast to the larger systemic dose (400 ng/kg body weight) of Gn-RH required to achieve the same results in urethane anaesthetized but otherwise identically treated rabbits. This suggests that although ovulation is not blocked by an anaesthetic dose of urethane (1.25 g/kg), the ovulatory response is altered in some way by the anaesthetic. When administered intraventricularly, the minimum dose of Gn-RH required to induce ovulation in anaesthetized animals was only 100 ng/kg body weight or 25% of the equivalent systemic dose. Systemically ineffective doses of Gn-RH (≤ 200 ng/kg body weight) also induced ovulation in the anaesthetized group when administered via the third cerebral ventricle.

All animals that ovulated did so between 13 and 16 h following Gn-RH administration and the number of ova recovered paralleled the number of ruptered follicles. A graded increase in the number of ova released with dosage of Gn-RH was not observed.

In this study, the smaller effective dose requirement for intraventricularly administered decapeptide supports the view that Gn-RH in the CSF circumvents the general circulation and reaches the portal vasculature directly via the median eminence.
Oestrogens and anti-oestrogens show dissociation between early uterine vascular responses and uterotrophic effects in mice
Authors: Arvidson Nils Gunnar , Terenius Lars
Published: December 2008

The structure-activity relationships of various natural and synthetic oestrogens, anti-oestrogens and some other steroid hormones with respect to early uterine albumin accumulation (EAV) was studied in spayed mice. The results were compared with the activity of these agents to produce a late anabolic response (LAR). The potency ranking order among the oestrogens with respect to EAV was found to be oestradiol-17β, > oestriol, > meso-hexoestrol, > erythro-deoxyhexoestrol, > ent-oestradiol-17β, > (-)methallenestril phenol. Generally the oestrogens were much more potent with respect to EAV than LAR. No correlation was found when the ability to promote EAV and LAR was compared.

Among other agents tested for effect on the EAV, progesterone, the synthetic progestogen, DU-41165 and the anti-hormones MER-25 and U-11100A (nafoxidine) showed no effect. However, hydrocortisone diminished EAV, while dihydrotestosterone increased EAV substantially.
Plasma prolactin concentrations during conception and the first ten weeks of human pregnancy
Authors: Lenton E. A. , Cripps K. , Sulaiman R. , Sobowale O. , Ryle M. , Cooke I. D.
Published: December 2008

Plasma prolactin concentrations were measured daily throughout 20 cycles in which conception occurred and for several weeks during early pregnancy. Thirteen of the pregnancies were 'spontaneous' (i.e. without exogenous pharmacological stimulation) and 7 occurred during either clomiphene or bromocriptine treatment. Prolactin concentrations were fairly stable throughout the conception cycles until shortly after the time of the first missed menses. From this time concentrations rose gradually to reach a mean concentration of 1250 mU/1 60 days after ovulation. However, there were marked fluctuations from day to day within individuals and considerable variation in the magnitude of the prolactin rise between subjects. Three subjects were mildly hyperprolactinaemic and although prolactin levels remained slightly elevated throughout the study period, this did not affect the outcome of pregnancies.
Testosterone and dihydrotestosterone in amniotic fluid and foeto-placental membranes from the guinea pig
Authors: Rigaudière N.
Published: December 2008

Testosterone (T) and dihydrotestosterone (DHT) in the amniotic fluid (AF) and foeto-placental membranes (FPM) (yolk-sac + amnion) from 180 male and female guinea-pig foetuses were determined by radioimmunoassay on days 28, 32, 36, 40, 44, 48, 52, 56, 60, 64 of gestation. In male foetus the evolution of androgens in the fluid is characterized by two sharp rises, the former at the time of sexual differentiation on day 32 (T = 219.1 ± 39.1 and DHT = 74.7 ± 10.0 fmol/ml) the latter, which affects only DHT, on day 52 (DHT = 68.5 ± 10.3 fmol/ml). In female foetus, AF T concentrations (mean = 36.3 fmol/ml) are comparable to the lowest T concentrations observed in male, while DHT concentrations (< 2.5 fmol/ml), are significantly lower than those observed in the male (mean = 28.9 fmol/ml) and without any overlap in the values. Thus, in guinea pig, DHT, but not testosterone allows to predict accurately the foetal sex at any stage studied. Testosterone and DHT are also present in FPM and their concentrations were comparable for male and female foetuses in most stages, values varying between 400 and 1600 fmol/g of tissue with a light predominance of DHT compared with T; in both sexes, general evolution of androgens is marked by a rapid drop between days 28 and 44 followed by a significant increase between days 44 and 64. Possible origins of androgens in AF and FPM are discussed.
2-Chloroadenosine increases calcium mobilization from mouse calvaria in vitro
Authors: Lerner Ulf , Fredholm Bertil B.
Published: December 2008

The effect of 2-chloroadenosine on bone resorption and on cyclic AMP formation in murine calvarial bones in vitro was investigated. 2-Chloroadenosine increased the release of 45Ca from the cultured bones, but had no effect on dead bones, indicating that the effect is cell mediated. The adenosine analogue remained in the medium for 48 h and caused a transient stimulation of the formation of cyclic AMP. The dose-response curve for the stimulatory effect on cyclic AMP accumulation was linear up to 10−4m. The dose-response curve for 45Ca release was linear from 3 × 10−7 m to 3 × 10−5 m but then showed a decline in the response. 8-Bromo cyclic AMP inhibited the release of 45Ca in 24 h cultures. The initial stimulatory effect on bone resorption by 2-chloroadenosine may therefore not depend on cyclic AMP. The level of inosine increased during culture indicating that adenosine is formed by bone tissue.
Evaluation of Prl secretion in elderly subjects
Authors: Rolandi Ermanno , Magnani Gianni , Sannia Antonello , Barreca Tommaso
Published: December 2008

Prl secretion was evaluated in 76 elderly patients (71–86 years) without endocrine disorders (38 men and 38 women) in basal conditions, after TRH, sulpiride and levodopa administration and during a 24 h period. An impaired Prl response to the administered drugs was found in the elderly women but not in the men. On the contrary, normal sleep-related serum Prl changes were found in the majority of the subjects studied. These results suggest that the pituitary gland can maintain a good Prl secretory pattern in the elderly.
Use of a single TSH-measurement after oral thyrotrophin releasing hormone: an economical and highly sensitive thyroid screening test
Authors: Platzer Rudolf , Wimpfheimer Claus , Bürgi Hans
Published: December 2008

The increment of serum TSH after thyrotrophin-releasing hormone (TRH) is usually considered an extremely sensitive thyroid test, particularly useful in borderline disturbances. We evaluated 195 patients by measuring serum TSH before and 3 h after 40 mg TRH po, and by various other thyroid tests.

We found a very tight correlation between the TSH-increment and the 3 h TSH. Thus the TSH-increment can reliably be estimated from the 3 h TSH. The Mann-Whitney test confirmed that the 3 h TSH identified thyroid dysfunction as well as the TSH-increment. The basal TSH can therefore be omitted and we propose the measurement of the 3 h TSH as an initial screening test. This single measurement economically excludes the many euthyroid patients sent for thyroid evaluation from further costly tests.
The effect of starvation and refeeding with oral versus intravenous glucose on serum 3,5-, 3,3'- and 3', 5'-diiodothyronine and 3'-monoiodothyronine
Authors: Jædig Steen , Faber Jens
Published: December 2008

The effect of complete fasting on the serum concentrations of the iodothyronines 3,5-diiodothyronine (3,5-T2), 3,3'-T2, 3', 5'-T2 and 3'-monoiodothyronine (3'-T1) was evaluated. Fourteen obese women underwent a complete fasting for 4 days. Caloric restriction resulted in the following serum hormone levels (before vs 3. day): T4: 103 vs 109 nmol/l (NS), T3: 1.83 vs 1.24 nmol/1 (P < 0.01), rT3: 0.276 vs 0.407 nmol/l (P < 0.01), 3.5-T2: 70 vs 70 pmol/l (NS), 3.3'-T2: 42 vs 39 pmol/l (P < 0.01), 3',5'-T2: 63 vs 93 pmol/l (P < 0.01), and 3'-T1 60 vs 116 pmol/l (P < 0.01). All subjects were refed with 200 g (800 kcal, 3350 kJ) d-glucose per day in divided doses for 2 days. Refeeding tended to normalize the changed iodothyronine concentrations and there was no difference whether the glucose was administered by the oral (n = 7) or the intravenous route.

It can be concluded that starvation in man is accompanied by profound changes in peripheral metabolism of the T2's and 3'-T1. There seems to be no qualitative difference of the effect on the thyroid hormone metabolism of d-glucose administered by the oral or the intravenous route.
Propranolol does not inhibit sulphonylurea-stimulated insulin secretion in patients with non-insulin dependent diabetes mellitus
Authors: Groop Leif , Tötterman Karl Johan
Published: December 2008

In a double-blind cross-over trial we compared the effects of placebo and propranolol on iv tolbutamide and oral glipizide-stimulated insulin secretion in 10 noninsulin dependent diabetics. The patients were randomly allocated for 2 weeks treatment with placebo and propranolol 80 mg twice daily. At the end of each period an iv tolbutamide test and an oral glipizide-glucose-test were performed.

Tolbutamide-stimulated insulin secretion was not affected by propranolol. There was no change in blood glucose levels during the iv tolbutamide test (IVTT), which excluded an effect of blood glucose on insulin secretion.

During the oral glipizide-glucose challenge propranolol decreased blood glucose at 60 min (P < 0.01) and increased C-peptide at 0 min (P < 0.01) and 30 min (P < 0.05) compared with placebo.

In contrast to earlier results obtained in animals and healthy subjects propranolol does not inhibit insulin- or C-peptide responses to sulphonylurea in patients with non-insulin dependent diabetes mellitus.
Therapeutic effect of tolbutamide in non-insulin dependent diabetes mellitus (NIDDM). Relation to beta-cell function
Authors: Damsgaard Else M. , Faber Ole , Frøland Anders , Iversen Steffen
Published: December 2008

The therapeutic effect of tolbutamide (1.5 g daily) in a random sample of patients with non-insulin dependent diabetes mellitus (NIDDM), was studied in a controlled, double-blind cross-over trial of 13 women and 6 men, aged 40–65 years and of 85–155% ideal body weight. The trial comprised C-peptide determinations during a standard carbohydrate rich meal followed by four periods of 3 months in which alternating tolbutamide and placebo were given.

From the beginning to the end of the treatment periods fasting blood glucose was reduced from 11.9 ± 1.1 (mean ± sem) to 10.0 ± 0.8 mmol/l (P < 0.025), glycohaemoglobin from 12.8% ± 0.7 to 11.3% ± 0.5 (P < 0.02) with a close correlation between fasting blood glucose and glycohaemoglobin (r = 0.87, P < 0.001). The observations during the first 3 months of study was not included in the calculations. Fasting C-peptide and fasting insulin concentrations were not significantly altered by tolbutamide treatment.

The effect of tolbutamide was inversely correlated to the C-peptide response to the standard test meal at the start of the trial (r = 0.76, P < 0.001), so that patients with the most pronounced beta-cell failure had the greatest therapeutical effect. The beta-cell response to the test meal could not identify patients, whose fasting blood glucose would be normalized by tolbutamide treatment.
Development of preovulatory follicles and oocytes during the oestrous cycle of mature and aged rats
Authors: Peluso J. J. , Hutz R. , England-Charlesworth C.
Published: December 2008

The percentage of viable granulosa cells and the viability of the oocyte of each antral follicle on each day of the oestrous cycle of mature and aged rats was determined by trypan blue exclusion and fluorescein diacetate assays, respectively. In mature rats, the number of mid-sized follicles (350–550 μm in diameter) increased from oestrus through di-oestrus. The percentage of viable granulosa cells increased in only mid-sized follicles which contained a viable oocyte. On pro-oestrus, two types of preovulatory follicles (> 550 μm in diameter) were observed in the mature pro-oestrous rat: those with a high granulosa cell viability (> 60%) and a viable oocyte and those with a lower percentage of viable granulosa cells (< 50%) and a non-viable oocyte. This suggests that in mature rats only viable oocytes would be ovulated since presumably, only those preovulatory follicles with a high percentage of viable granulosa cells are able to ovulate.

In aged rats, preovulatory-sized follicles were present on each day of the cycle. The percentage of viable granulosa cells within those preovulatory-sized follicles with nonviable oocytes increased on met-oestrus, decreased on di-oestrus and increased by pro-oestrus. This pattern resulted in the development of 3 to 4 preovulatory follicles per ovary with all preovulatory-sized follicles possessing a high percentage of viable granulosa cells regardless of the functional state of the oocyte. It is proposed that in aged rats, all the preovulatory follicles would ovulate but many of the ovulated oocytes would be defective. This mechanism would account for the lower fertility of these older animals.
The aging Leydig cell: VI. Response of testosterone precursors to gonadotrophin in men
Authors: Murono E. P. , Nankin H. R. , Lin T. , Osterman J.
Published: December 2008

The effects of a single im injection of human chorionic gonadotrophin (hCG) on circulating testosterone precursor levels at 0, 1–6, 24, 48 and 72 h were examined in normal young adults (mean age 34 years) and normal aged men (mean age 74 years). Basal 08.30–09.00 h concentrations of androstenedione and dehydroepiandrosterone were lower in aged men while progesterone levels were not significantly different from young men. A significant biphasic increase of circulating progesterone was observed in young men, characterized by an early peak at 2 h (33% above basal) and a secondary peak at 24 h (49% above basal). In old men there were no increases in circulating progesterone levels following hCG treatment during the early (1–6 h) or late (24–72 h) periods. There were not discernable increases in circulating dehydroepiandrosterone levels following hCG administration in both groups of men. Androstenedione levels in young men did not change during the first 6 h following hCG but increased significantly at 48 and 72 h, while in old men there was a small peak at 4 h (which was not statistically significant) and a secondary significant rise at 48 and 72 h. However, early and late stimulated absolute levels for androstenedione were lower in the aged population. Thus, there are differences in precursor concentrations in the basal state and in response to hCG in aged men.
Effect of various drugs on the binding of thyrotrophin to thyroid plasma membranes
Authors: Baba Yasuto , Nakao Yoshinobu , Kishihara Michizo , Kobayashi Nobuhisa , Kimoto Hiroyuki , Matsukura Shigeru , Fujita Takuo , Kuma Kanji
Published: December 2008

Effects of enzyme inhibitors and membraneactive drugs on the binding of 125I-labelled thyroidstimulating hormone (TSH) to human thyroid membranes and membrane adenylate cyclase (AC) activity were studied. FOY®, a synthetic polyvalent proteolytic enzyme inhibitor, Trasylol®, α- and β-adrenergic blocking agents, tranquilizers, anti-histamines and polyene antibiotics enchanced TSH binding in a dose-dependent manner, whereas selective enzyme inhibitors and adrenergic stimulating agents had no effect. Both propranolol and FOY inhibited basal and TSH stimulated AC activity of thyroid membranes. FOY, as well as propranolol was found to have protective effects on hypotonic erythrocyte lysis. These results suggest that propranolol and FOY increased TSH binding by the same mechanism, probably the so-called membrane-stabilizing effects. Although the detailed mechanisms underlying the increased TSH binding by these drugs remain unknown, they may change the membrane structure, thereby enhancing the TSH receptor affinity.