bluuebunny/crossref_metadata_2025 huggingface dataset:
The incidence of occult thyroid disease associated with thyroid antibodies identified on routine autoantibody screening
Authors: Tanner A. R. , Scott-Morgan Lindsay , Mardell R. , Lloyd R. S.
Published: December 2008

The presence of thyroid microsomal and/or thyroglobulin antibodies has been recorded over a 2 year period in 15000 consecutive autoimmune profile requests. Where there had been no initial clinical suspicion of thyroid diseases, 332 requests showed positive thyroid antibodies, and of these 63 (19%) had abnormal in vitro thyroid function tests (TFT). No differences were observed between the abnormal and normal groups with respect to the presence of different autoantibodies or to the age and sex distributions. Of these subjects with clinically unsuspected hypothyroidism but with abnormal TFTs, 29% were commenced on thyroxine therapy and experienced a symptomatic improvement, 25% remain well on no therapy and 9% continue on no treatment but with symptoms possibly attributable to hypothyroidism. 3% became clinically hypothyroid during a follow-up period of 2 years. 5% died of unrelated causes and there was inadequate follow-up information on the remainder. This study provides further confirmation that when thyroid antibodies, and in particlar thyroid microsomal antibody, are found unexpectedly, a significant proportion of patients will have biochemical evidence of hypothyroidism and may benefit from appropriate treatment.
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

Equimolar concentrations of [4-14C]oestriol and [6,9-3H2]oestriol 16α-monoglucuronide were simultaneously perfused through isolated rat livers. Oestriol was hydroxylated to 2-hydroxyoestriol and 6ξ-hydroxyoestriol; 2-hydroxyoestriol was further methylated to 2-methoxyoestriol. Oxidoreduction of oestriol led to the formation of 16α-hydroxyoestrone, 16-oxooestradiol-17β and 16-epioestriol. In addition, two dehydroxylation products, namely oestrone and oestradiol-17β were found. The metabolites formed from oestriol were partly conjugated to monoglucuronides, monosulphates and sulphoglucuronides.

About 80% of the oestriol perfused was hydroxylated at C-atom 2. Most of the 2-hydroxyoestriol formed was either methylated (about 37%) or sulphated (about 55%). Only small amounts (less than 2%) of the catecholoestrogens formed were methylated as well as sulphated. The 2-hydroxyoestriol monosulphates accumulated in the liver. After their conjugation with glucuronic acid, the double conjugates formed were immediately excreted into the bile. In fact, 2-hydroxyoestriol 16α-monoglucuronide 2(3?)-monosulphate comprised by far the main biliary metabolite of [4-14C]oestriol, followed by oestriol 16α-monoglucuronide and 2-methoxyoestriol 16α-monoglucuronide.

No tritiated sulphoglucuronides were detected, thus indicating that the monosulphates are the immediate precursors of the double conjugates. [6,9-3H2]Oestriol 16α-monoglucuronide was metabolised only to a small extent. After its uptake into the liver more than 90% of this conjugate was secreted unchanged into the bile. The remaining part was hydrolysed; the oestriol liberated followed the same metabolic reactions as those found for [4-14C]oestriol. This indicates that the 16α-glucuronide of oestriol is not metabolised to any appreciable extent.
17α-Hydroxylase deficiency syndrome associated with bilateral streak gonads and impaired development of Müllerian ducts derivatives
Authors: de Gennes Jean-Luc , Jambart Sélim , Turpin Gérard , Elkik François , Roger Marc
Published: December 2008

We report severe 17α-hydroxylase deficiency in a 17 year-old black girl with 46,XX genotype. The diagnosis was suspected because of primary amenorrhoea, absence of sexual maturation, hypertension and hypokalaemia with renal potassium wasting. Endocrine investigation revealed low basal levels of all steroid hormones which require 17α-hydroxylation for biosynthesis (i.e. glucocorticoids, androgens and oestrogens). No increase in their basal levels was seen following adrenal stimulation, indicating a severe block. Plasma concentrations of ACTH, FSH and LH were elevated as were progesterone, 11-deoxycorticosterone and corticosterone. Plasma renin activity was suppressed and aldosterone levels were very low. After 4 months of glucocorticoid replacement therapy, aldosterone was still low, even though the suppression was otherwise effective. Our case is unusual because bilateral streak gonads and impaired development of Müllerian ducts derivatives were also present. To our knowledge, a similar case has never been reported before.
Diurnal rhythm of total and free concentrations of serum corticosterone in the rat
Authors: D'Agostino JoBeth , Vaeth Gregory F. , Henning Susan J.
Published: December 2008

Daily variations in serum concentrations of total and free corticosterone and corticosteroid-binding globulin (CBG) were determined at 4 h intervals in male rats maintained on a 12:12 h light/dark cycle (lights on at 05.00 h). Total corticosterone concentrations exhibited a classical rhythm with peak values occurring at the onset of dark (17.00 h). Serum CBG concentrations displayed daily fluctuations but these appeared to be non-rhythmic in nature.

The % free corticosterone exhibited a diurnal rhythm with peak values occurring during the dark phase. When absolute concentrations of free corticosterone were calculated, the profile could be superimposed on that of total corticosterone with the zenith at the onset of the dark phase (17.00 h) and the nadir coinciding with the onset of light (05.00 h). These data suggest that the primary determinant of the rhythm in free corticosterone concentrations is the daily rhythm in total corticosterone.
Placental secretion of prolactin, ACTH and immunoreactive β-endorphin during pregnancy
Authors: Demura Reiko , Odagiri Emi , Yoshimura Masayo , Jibiki Kazuko , Adachi Tomoko , Shirota Mariko , Demura Hiroshi , Shizume Kazuo , Oouchi Hiroko
Published: December 2008

The placental secretion of Prl, ACTH and immunoreactive (IR)-β-endorphin were examined in early and later pregnancy with a perfusion method and by determining tissue concentrations of these hormones. Prl was secreted mainly from decidual tissue during 5–6 h long perfusions. Tissue concentrations of Prl were also significantly higher in decidual than in trophoblastic tissues. In contrast, the tissue concentrations of hCG, hPL, ACTH and IR-β-endorphin were significantly higher in trophoblastic than in decidual tissues. Production of hCG and hPL was predominantly demonstrated in trophoblastic tissues by the perfusion method but ACTH and IR-β-endorphin were too low to be detected by perfusion.
Binding of 5α-dihydroprogesterone to proteins in human pregnancy serum
Authors: Lea Oscar A.
Published: December 2008

The binding of 5α-dihydroprogesterone (DHP)1 to proteins in pregnancy serum has been investigated and compared with the binding of progesterone. Characteristic properties of the DHP-serum protein interaction were unsaturability, low affinity and poor complex stability. Fractionation of serum using a variety of protein separation techniques, revealed that DHP interacts with several proteins. At low temperature (0–4°C) albumin appeared to be the principal binding component whereas higher temperatures seemed to favour binding to β-lipoproteins and α2-macroglobulin. Binding to specific binding proteins such as the corticosteroid binding globulin (CBG) and the sex hormone-binding globulin, (SHBG) were detectable but appeared to be quantitatively unimportant.

Progesterone showed a similar multicomponent interaction but differed from DHP in the extent of binding to CBG. Binding of either hormone to the α1-acid-glycoprotein was negligible.

The present study shows that the high endogenous DHP levels present in pregnancy sera are caused by factors other than high affinity protein binding.
Correlation of the HLA-A1,B8 haplotypes with circulating autoantibodies in a family with increased incidence of autoimmune disease
Authors: Valenta Lubomir J. , Bull Robert W. , Hackel Emanuel , Bottazzo Gian Franco
Published: December 2008

Two cases of Addison's disease, two cases of scleroderma, three cases of primary hypothyroidism possibly due to Hashimoto's thyroiditis, three cases of diabetes mellitus, and two cases of ovarian failure and secondary amenorrhoea were diagnosed in a single family. In 44 members of four generations of the family including all the diseased, we have performed HLA typing and measurement of circulating autoantibodies. All diseased patients were older than 12 years, all possessed HLA B8 antigen, and all but two showed specific autoantibodies in their serum. In contrast, none of the family members without HLA B8 developed any of the autoimmune diseases in spite of the fact that in 13 of them some circulating autoantibodies were demonstrable in the serum. It is concluded that genetic factors play an essential role in the development of autoimmunity in the studied family. The individuals acquire circulating autoantibodies as they develop the disease. Environmental factors play a secondary role as evident from the age dependence. HLA typing can become an important diagnostic tool in identifying the individuals at a risk of autoimmune disease. Detection of circulating serum autoantibodies alone correlated poorly with the autoimmune disease.
Catecholamine turnover in the brain and the regulation of luteinizing hormone and corticosterone in starved male rats
Authors: Pirke K. M. , Spyra B.
Published: December 2008

The effect of starvation was studied in male Wistar rats. After only 2 days of food deprivation, LH concentrations in serum are greatly suppressed, while a significant increase in plasma corticosterone occurs after 5 days' starvation. The noradrenaline and dopamine turnover in the basal hypothalamus is decreased after 2 days. The catecholamine turnover is also reduced in the preoptic area, and in the median eminence. Injection of the catecholamine precursor l-dopa (100 mg/kg) can prevent the increase of plasma corticosterone, but not the decrease of LH. The α-agonist clonidine (150 μg/kg), but neither the β-agonist salbutamol (0.5 mg/kg), nor the dopamine agonist apomorphine (1.0 mg/kg) can prevent the starvation induced corticosterone increase. The decrease of plasma LH is not influenced by the dopamine or noradrenaline agonists. From these data, it appears that a decreased activity of noradrenergic neurons may be responsible for the corticosterone increase in the plasma of starved rats.
Prl, TSH, GH and LH responses to metoclopramide and breast-feeding in normal and hyperprolactinaemic women
Authors: Andersen A. Nyboe , Tabor Ann
Published: December 2008

In order to evaluate whether hyperprolactinaemic patients have an increased or decreased central dopaminergic tonus, we compared the serum Prl, TSH, GH and LH responses to metoclopramide (10 mg iv) and to breast-feeding in normal women (n = 8) and hyperprolactinaemic patients (n = 8).

Prl increments to metoclopramide were significantly (P < 0.05) impaired in hyperprolactinaemic patients. Serum TSH increased significantly after metoclopramide both in normal and hyperprolactinaemic patients (P < 0.025), but no significant differences were found between the two groups regarding TSH, GH or LH levels.

Hyperprolactinaemic pateints had no acute response to suckling while significant increments of Prl and GH (P < 0.025) occurred in normal women.

Our data indicate that the central dopaminergic tonus was not altered in hyperprolactinaemic patients, but showed regulatory dysfunction of both Prl and GH. The concept of a dopaminergic inhibition of TSH secretion was confirmed.
Testosterone inhibition of LRH-induced luteinizing hormone release by cultures of rat anterior pituitary cells: effect of inhibitors of steroid 5α reductase
Authors: Leveque N. W. , Grotjan H. E.
Published: December 2008

Cultures of rat anterior pituitary cells were utilized to examine the role of 5α reduction in the inhibitory action of testosterone on LRH-induced LH release. Cultures were pre-treated with steroids for 48 h and then incubated 6 h with steroids plus 5 × 10−10 m LRH, the approximate EC50 for LH and FSH release. Testosterone inhibited LRH-induced LH release with an IC50 of approximately 2 × 10−10 m. However, even relatively high concentrations of testosterone did not completely inhibit LRH-induced release. Testosterone (and dihydrotestosterone) appeared to antagonize LRH-induced LH release but did not markedly affect 48 h basal release or LH synthesis as judged by the quantity of LH released plus that remaining intracellularly. Progesterone (10−6 M) and heparin (1000 U/ml) were used as inhibitors of anterior pituitary steroid 5α reductase. Progesterone, when combined with testosterone, markedly shifted the testosterone inhibition curve to the right (approximately 340-fold) but did not shift the dihydrotestosterone inhibition curve. Heparin also slightly shifted the testosterone inhibition curve (approximately 2.4-fold) to the right. These observations support the hypothesis that the mechanism of action of testosterone on the anterior pituitary involves 5α reduction.
The influence of vasopressin on oxytocin-induced changes in urine flow in the male rat
Authors: Forshing Mary L. , Brimble M.J. , Balment R. J.
Published: December 2008

Oxytocin administration in rats infused with hypotonic saline is associated with a saliuresis and altered renal water excretion. The role of vasopressin in determining the pattern of oxytocin-induced changes in urine flow was investigated in Long Evans and vasopressin-deficient Brattleboro rats, which exhibit contrasting diuretic and antidiuretic responses to oxytocin. Ethanol anaesthesia and water loading in Long Evans suppressed plasma vasopressin levels and was associated with an antidiuretic response to oxytocin. Vasopressin administration in the Brattleboro rat reversed the oxytocin-induced antidiuresis normally observed in vasopressin dificiency. These results taken with previous observations, have been interpreted as indicative that oxytocin acts as a weak agonist at the renal vasopressin receptor. When plasma vasopressin is suppressed or absent oxytocin acts as a weak antidiuretic agent, but in the presence of higher vasopressin levels a diuretic response to oxytocin is seen which follows displacement of vasopressin, the more potent antidiuretic agent, from the renal receptor.
Familial elevations of total and free thyroxine in healthy, euthyroid subjects without detectable binding protein abnormalities
Authors: Maxon Harry R. , Burman Kenneth D. , Premachandra Bhartur N. , Chen I-Wen , Burger Albert , Levy Phillip , Georges Leon P.
Published: December 2008

Elevations of serum thyroxine without thyrotoxicosis or binding protein abnormalities have been documented in 8 of 13 family members, representing 4 generations. This syndrome appears to represent an elevated threshold for the amount of free thyroxine substrate required to maintain adequate T3 production form the peripheral monodeiodination of T4. It reiterates the need for a prudent re-evaluation of all clinically euthyroid patients with elevated serum thyroxine concentrations before concluding that they are indeed thyrotoxic.
Standardization of the radioreceptor assay against anti-thyrotrophin receptor antibodies in Graves' disease
Authors: de Bruin T. W. A. , Krol M. C. , van der Heide D.
Published: December 2008

We studied the possibility of standardizing the radioreceptor assay for the detection of anti-thyrotrophin receptor antibodies, also called thyrotrophinbinding inhibitor immunoglobulins (TBII), to circumvent the problem of inter-assay variability in TBII index calculations. We developed a procedure for conversion of the thyrotrophin-binding inhibition caused by standard amounts (10 mg IgG/ml) of 1.6 m ammonium sulphate precipitates into thyrotrophin-equivalents, i.e. the amount of thyrotrophin required to cause the same thyrotrophin-binding inhibition. We were able to determine a normal range for thyrotrophin-binding inhibition which exhibited little inter-assay variability and was applicable to individual radioreceptor assays. The normal range, expressed in thyrotrophin-equivalents or the logarithm of μU thyrotrophin, was 2.616–3.645, which corresponds to 413–4420 μU. The thyrotrophin-binding inhibition by 1.6 m ammonium sulphate precipitates from sera of 17 untreated patients with Graves' disease was also expressed in thyrotrophin-equivalents. For 15 patients (88%) the thyrotrophin-equivalent values were above the normal range, whereas only 10 patients (59%) had a positive TBII index (using the same sample). This indicated that 5 patients had anti-thyrotrophin receptor antibodies in spite of their negative TBII index. Standardization based on the IgG content of the test samples therefore seems to be imperative. Pig serum 1.6 m ammonium sulphate precipitates, which were tested in a porcine assay system, yielded thyrotrophin-equivalent values that corresponded closely to the normal range for the human assay system, suggesting that the normal range of thyrotrophin-binding inhibition is in the same order of magnitude in porcine and human assay systems.
Enhancement of gonadotrophin induced 17,20-lyase suppression one week after human chorionic gonadotrophin priming
Authors: Smals A. G. H. , Boers G. H. J. , Roose P. H. C. , Pieters G. F. F. M. , Beex L. V. A. M. , Kloppenborg P. W. C.
Published: December 2008

A single injection of 1500 IU of human chorionic gonadotrophin (hCG) in normal men, induced a block in the conversion of 17-hydroxyprogesterone (17-OHP) to testosterone (T) which reached its maximum 24 h after hCG loading. One week after hCG administration both basal 17-OHP (3.8 ± 0.6 vs 5.1 ± 0.5 nmol/l, P < 0.02) and T levels (15.1 ± 1.7 vs 18.5 ± 2.3 nmol/l, P < 0.05) were about 20% lower than before hCG exposure. The ratio 17-OHP to T (0.29 ± 0.04 vs 0.31 ± 0.04, P > 0.10) was however similar, suggesting recovery from the prior 17,20-lyase suppression at a lower overall capacity of T synthesis.

hCG administration one week after the priming dose elicited an increase in the ratio 17-OHP to T, which was about twice as high as after the first hCG injection.

Together the data suggest: 1) suppression of testicular steroidogenesis proximal to 17-OHP one week after hCG priming, 2) enhanced hCG induced 17,20-lyase suppression one week after hCG exposure.
Instant growth inhibition by low dose oestrogens in excessively tall boys
Authors: van den Bosch John S. G. , Smals Anthony G. H. , Pieters Gerlach F. F. M. , Valk Ignace M. , Kloppenborg Peter W. C.
Published: December 2008

A major problem in the androgen treatment of escessive height in boys is acceleration of growth velocity especially in the early stages of therapy. Oestrogen treatment in tall girls, in contrast, instantly decelerates growth velocity, probably by its plasma somatomedin lowering effect. As oestrogen administration in male subjects causes a similar somatomedin depression and immediate growth inhibition is also wanted in the treatment of excessive height in boys, the effect of short-term low dose oestrogen therapy (ethinyloestradiol, Ee, Lynoral®, 0.050 mg daily) on growth was studied in 10 constitutionally tall boys.

During oestrogen therapy three week ulnar growth rate (TUG-rate) dropped instantly from 0.84 ± 0.42 to 0.33 ± 0.27 mm (P < 0.02) within 6 weeks. Three week body growth rate also changed significantly from 0.48 ± 0.23 to 0.12 ± 0.37 cm during oestrogen loading (P < 0.05). The magnitude of the latter changes, however, allows only evaluation of the whole group, whereas changes in TUG-rates far exceeded the limits of confidence in most individual boys.

Growth deceleration during Ee was accompanied by a significant decrease in serum alkaline phosphatase activities (from 299 ± 72 U/l before to 240 ± 79 U/l during Ee, P < 0.01), plasma calcium (from 2.45 ± 0.06 to 2.35 ± 0.05 mmol/l during Ee, P < 0.05) and plasma testosterone levels (from 392 ± 128 ng/100 ml before to 27 ± 7 ng/100 ml during Ee, P < 0.005). Within 2 months after stopping Ee administration plasma testosterone levels were normal again (432 ± 282 ng/100 ml).

Testicular size was not affected. Mild reversible gynaecomastia, however, was present in all boys.

The results demonstrate an instant growth decelerating effect of low dose oestrogen administration in tall boys reminiscent to the findings in tall girls under the same low dose regimen. Furthermore these data provide a theoretical base for combining androgens and oestrogens in the early stages of treatment of excessive height in boys in order to antagonize the initial growth accelerating effect of androgens alone.
Hyperprolactinaemia and breast disease as evaluated by xeromammography
Authors: Calhaz-Jorge C. , Cunha C. , Nunes M. C. P. , Sobrinho L. G.
Published: December 2008

This report compares the xeromammographic patterns of 35 patients with hyperprolactinaemia and 70 (age-matched) normoprolactinaemic controls. It is shown that nulliparous patients have less frequent mammary dysplasia and more patterns of involution than the nulliparous controls. The groups of parous patients and parous controls were similar to each other and both had more involutions and less dysplasia than the nulliparous controls. Hyperprolactinaemia in parous women is not associated with any changes in the xeromammographic breast patterns as compared to parous controls. The changes described in hyperprolactinaemic patients can be understood in terms of their low oestrogenic activity.
The incidence and pathogenesis of hyperlipidaemia in 16 consecutive acromegalic patients
Authors: Takeda Ryoyu , Tatami Ryozo , Ueda Kosei , Sagara Hosaku , Nakabayashi Hajime , Mabuchi Hiroshi
Published: December 2008

Serum lipids were analyzed in 16 patients with active acromegaly. Of these 62.5% had hyperlipidaemia defined as exceeding the 90% fiducial limits of normal controls. The mean serum cholesterol (5.50 mmol/l) and triglyceride (4.09 mmol/1) levels of the patients were significantly higher than those of age-matched normal controls. Type V hyperlipoproteinaemia was observed in two cases and type III hyperlipoproteinaemia in one. There was no difference in the incidence of diabetes between the normolipidaemic (n = 6) and hyperlipidaemic (n = 10) groups. Serum levels of growth hormone in hypercholestelaemic patients (n = 3) were significantly higher than those of normolipidaemic patients and combined hyperlipidaemic patients (n = 5) tended to have higher levels of growth hormone than normolipidaemic patients.

In cases developing type III or type V hyperlipoproteinaemia, the activity of hepatic triglyceride lipase or lipoprotein lipase was decreased, but it increased when serum GH levels fell after therapy for acromegaly.

It is suggested that 1) growth hormone may play some role on the pathogenesis of hyperlipidaemia associated with acromegaly, and 2) growth hormone has an inhibitory effect on H-TGL and LPL, and so hyperlipoproteinaemia in some cases of acromegaly might be caused by low H-TGL or LPL activity resulting from high growth hormone levels.
Triiodothyronine and thyroxine treatment of diffuse non-toxic goitre evaluated by ultrasonic scanning
Authors: Perrild H. , Hansen J. M. , Hegedüs L. , Rytter L. , Holm B. , Gundtofte E. , Johansen K.
Published: December 2008

Ultrasonic scanning has been used to estimate changes in goitre size during and after treatment with a daily dose of either 100 μg thyroxine (T4) (n = 30), 150 μg T4 (n = 33), 200 μg T4 (n = 17) or 60 μg triiodothyronine (T3) (n = 30) for one year in patients with diffuse non-toxic goitre. The thyroid volume was measured before and every 3 months during and 3 months after withdrawal of therapy. All 4 treatments resulted in a decrease in goitre size after 3 months' therapy (P < 0.05) but only in the patients given 200 μg T4 and 60 μg T3 was the decrease long lasting during additional 9 months' therapy. The mean reduction in thyroid volume after 12 months therapy was 30 ± 26 sd and 22 ± 30 (sd)%, respectively. The free-T4-index was found significantly raised throughout the treatment with all three T4 doses, whereas the free-T3-index did not change. During treatment with 60 μg T3 no persistent rise in free-T3-index was seen while free-T4-index was decreased all 12 months.

No increase in goitre size was observed 3 months after withdrawal of the T3 therapy (n = 15), whereas all goitres in the T4 treated groups had returned to the pre-treatment values at that time. No rebound phenomenon was observed. The serum T3 and T4 levels were normalized 3 months after withdrawal in all four groups. Seven out of 8 patients on 200 μg T4 daily and 20 out of 25 patients on 60 μg T3 daily had no TSH response to TRH (200 μg iv) after 3 months' therapy. Forty-three out of 61 patients in the 4 groups showed no TSH response to TRH after 3 months' therapy. Only the group of patients showing no TSH response to TRH after 3 months' treatment had a significant decrease in goitre size in contrast to the group with a positive response to TRH.
The effects of pituitary hormones on hepatic drug metabolism in the rat
Authors: Skett Paul , Young Colin
Published: December 2008

Sex differences exist in the hepatic microsomal metabolism of drugs in the rat. These differences have been shown to be related to the presence of androgen in the male and the pituitary gland in the female. The present study was designed to identify the pituitary 'feminizing factor' by continuously infusing hormones via an osmotic mini-pump. Rat somatotropin and prolactin mimicked somewhat the 'feminizing' effect of pituitary extract infused into male animals while human somatotropin, which binds to both lactogenic and somatogenic receptors in rat liver, completely reversed the effect of hypophysectomy of female rats with respect to most of the parameters studied. It thus appears that the somatogenic/lactogenic receptors in the rat liver are involved in the maintenance of the sex differences in drug metabolism but the identity of the hormone that normally acts on these receptors in the rat is still uncertain.
Cortisol, 17α-OH-progesterone and androgen responses to a standardized ACTH-stimulation in different stages of the normal menstrual cycle
Authors: Kruyt N. , Rolland R.
Published: December 2008

The release of cortisol, 17α-OH-progesterone, androstenedione and testosterone during a standardized ACTH-stimulation test was investigated in three different stages of the normal menstrual cycle, to conclude if there is any stage dependency on the release of these hormones.

No statistically significant differences were observed between the three stages concerning cortisol and testosterone increase. The increase of androstenedione in the pre-ovulatory stage was significantly higher than that seen during the early follicular phase of the cycle.

The increase of 17α-OH-progesterone in the luteal phase was significantly less than that of both the early and late follicular stages of the cycle.

Progesterone levels showed a small, but significant increase after ACTH-stimulation, in both the early and late stage of the follicular phase. However, the levels remained within the normal range of the follicular phase. In the luteal phase no increase was seen after ACTH-stimulation. Oestradtiol-17β levels did not change at all after ACTH-stimulation.

The stage dependency of androstenedione and 17α-OH-progesterone is discussed. The described stage-dependency different increase of 17α-OH-progesterone release can be of importance when the results of ACTH-tests are evaluated to detect carriers of congenital adrenal hyperplasia.
Inhibition of rat follicular androgen synthesis by dibutyryl cyclic AMP
Authors: Ekholm Carl , Hillensjö Torbjörn , Thelander Harriet , Ahrén Kurt
Published: December 2008

LH exerts a biphasic effect on rat follicular steroidogenesis: an initial general stimulation of steroidogenesis later followed by an inhibition of androgen and oestrogen synthesis. It is known that the stimulation by LH of steroidogenesis is mediated by cAMP. The present paper examines the role of cAMP in the late inhibitory phase of steroidogenesis.

Pre-ovulatory follicles were isolated from PMSG treated immature rats and incubated in modified bicarbonate buffer for different time periods. The accumulation of progesterone (P), androstenedione (A), testosterone (T) and oestradiol-17β (E2) in the medium was measured. Addition of dibutyryl cAMP (dbcAMP, 1 mm) to the medium caused a prolonged increase in P accumulation for 10 h while A and E2 accumulation was stimulated only for 4–6 h whereafter the levels were sustained. The pattern was identical to that produced by LH (10 μg/ml) in vitro.

In a second type of experiments follicles were pre-incubated for 6 h with or without LH or dbcAMP and then transferred for a second 2 h incubation, in the presence or absence of unlabelled 17-hydroxyprogesterone (17-OHP) or T (1 μg/ml). Follicles pre-incubated in plain medium increased their formation of A and T in the presence of 17-OHP, while follicles exposed to LH or dbcAMP did not. Addition of T caused a similar increase in E2 formation in all groups (control, LH and dbcAMP). It is concluded that since dbcAMP mimicked the entire response of follicular steroidogenesis normally elicited by LH, cAMP seems to be the physiologic mediator of LH, both on the early stimulatory and on the late inhibitory phase of pre-ovulatory follicular steroidogenesis.
Release and synthesis of FSH by pituitary glands of female rats in vitro
Authors: Jenner A. A. J. , de Koning J. , van Rees G. P.
Published: December 2008

Anterior hemi-pituitary glands from intact female and ovariectomized (OVX) rats were incubated with or without a maximally effective dose of LRH. During an 8 h incubation, LRH-stimulated release of FSH by pituitary glands from intact rats was biphasic: an initial slow rate of release and, from 2 to 8 h, an enhanced rate of release. Basal release was low up to 4 h, after which a marked increase of the rate of release was measured: from 6 to 8 h there was no difference between the rates of basal and LRH-stimulated release. Basal and LRH-stimulated release of FSH by pituitary glands from OVX rats were high and approximately constant during an 8 h incubation.

Both basal and LRH-stimulated release by glands from intact as well as OVX rats were protein synthesis dependent. During the incubations an LRH-independent synthesis of FSH was measured. The results suggest that this synthesis is involved, either directly or indirectly, in increasing the rate of basal release of FSH after 4 h.

A comparison of release and synthesis of FSH with those of LH reveals characteristic differences.
Thyroid associated components in serum during normal pregnancy
Authors: Skjöldebrand Lottie , Brundin Jan , Carlström Anders , Pettersson Tom
Published: December 2008

Thyroxine-binding globulin (TBG), thyroxine-binding pre-albumin (TBPA), thyroxine (T4), free-T4, triiodothyronine (T3), and thyroid-stimulating hormone (TSH) were studied throughout apparently normal pregnancy in 290 cases grouped in 2 week intervals. TBG increased to a plateau level reached in the 24th week and was hereafter unchanged until term. T4 showed an increase until the 16th week of pregnancy and levelled off to a constant level for the rest of the pregnancy. Free-T4 declined to almost subnormal values for the non-pregnant state which was reached around the 20th week of pregnancy. T3 showed a slight and definite increase in the beginning of pregnancy and levelled off to a constant value after the 14th week. TSH increased towards the end of pregnancy also showing its maximum during the last 4 weeks. TBPA showed constant values throughout pregnancy. The results are discussed in view of the use of modern techniques and previously missing data in literature (TBPA).
Familial hyperthyroidism without evidence of autoimmunity
Authors: Thomas Jean-Louis , Leclere Jacques , Hartemann Pierre , Duheille Jean , Orgiazzi Jacques , Petersen Meryl , Janot Christian , Guedenet Jean-Claude
Published: December 2008

Thirty-four members of a single family were studied and 9 of them were found to be suffering from hyperthyroidism associated wiht diffuse goitre. Exophthalmos was absent and transmission seemed to be independent of HLA type. Four of the 9 were studied prior to treatment but in all cases serum immunoglobulin levels were normal, antithyroglobulin and antimicrosomal antibodies absent, thyroid stimulating antibodies negative and the lymphocyte transformation responses to mitogens not different from those of controls. The results of testing the euthyroid family members were similarly negative, except in the case of a woman with type I diabetes mellitus who showed a low titre of antimicrosomal antibody.

Seven of the patients underwent subtotal thyroidectomy. Lymphocytic infiltration of the excised portion was rarely present. Four of the glands were subjected to immunofluorescent and electron microscopy but neither immunosecreting cells nor immune complex deposits were found.

These results point to the existence of a non-autoimmune form of goitrous hyperthyroidism, different from Graves' disease.
Inhibition of insulin secretion by l-thyroxine and d-thyroxine treatment in rats under the influence of drugs affecting the adrenergic nervous system
Authors: Lenzen S. , Kücking H.
Published: December 2008

Both l-thyroxine and d-thyroxine induced an inhibition of glucose-induced insulin secretion with comparable time- and dose-dependent characteristics. l-thyroxine was ten times more potent than d-thyroxine. While l-thyroxine and a ten times higher dose of d-thyroxine had a similar potency in inducing hyperthermia and hypocholesterolaemia, hyperglycaemia in response to d-thyroxine was less pronounced than in response to l-thyroxine. This difference may be explained by a greater depletion of liver glycogen stores and consequently more limited capacity for provision of glucose for the circulation. The results support the view that the differences between l-thyroxine and d-thyroxine are quantitative. Adrenergic contribution to l-thyroxineand d-thyroxine-induced inhibition of insulin secretion by rat pancreas is apparently of minor importance. Treatment of the rats with propranolol as well as with reserpine or 6-hydroxydopamine did not alleviate l-thyroxine- or d-thyroxine-induced inhibition of insulin secretion by rat pancreas.
Effects of α-adrenergic stimulation and blockade on parathyroid hormone responses to β-adrenergic agonists in cattle
Authors: Blum J. W. , Fischer J. A. , Binswanger U.
Published: December 2008

Experiments were designed to investigate the effect of α-adrenergic stimulation on parathyroid hormone (PTH) responses to isoproterenol (ISO). In addition, PTH responses to adrenaline (A) and hypocalcaemia were studied with and without α-adrenergic blockade by phentolamine. Infusions of phenylephrine (a 'pure' α-adrenergic agonist) did not modify basal PTH levels and PTH responses to ISO infusions, whereas the heart rate response to ISO was reduced (P < 0.05). The results demonstrate that α-adrenergic stimulation by phenylephrine does not reduce PTH responses to β-adrenergic agonists. In response to phentolamine the heart rate increased and plasma levels of Ca and Ca++ decreased. Plasma PTH concentrations were slightly but not significantly raised and PTH responses to adrenaline (P < 0.05), but not to hypocalcaemia, were enhanced. The potentiation of PTH responses to A in the presence of phentolamine may have been due to inhibition of α-adrenergic properties of A. It may have been also, in part, the consequence of the hypocalcaemia, which is known to augment PTH responses to A.
Catecholamine stimulation of cyclic AMP and progesterone production in rat corpora lutea of different ages
Authors: Norjavaara Ensio , Selstam Gunnar , Ahrén Kurt
Published: December 2008

In vitro effects of catecholamines (adrenaline and noradrenaline) and adrenergic antagonists on adenosine 3′,5′-cyclic monophosphate (cAMP) and progesterone production by rat corpora lutea (CL) of different ages (1–8 days old) were studied. To obtain defined ages of CL a pregnant mare's serum gonadotrophin (PMSG) model was used. The effect of catecholamines on cAMP decreased with luteal age while the effect on progesterone production was maximal on 5 day old CL. The β-blocker propranolol inhibited the effects of catecholamines in concentrations around 10−5 m. The effects of LH could only be inhibited with higher doses of propranolol known to exert unspecific effects. These results support the theory that LH and catecholamine effects on rat corpora lutea are mediated through different receptors.
Calcium antagonists and hormone release
Authors: Barbarino Antonino , De Marinis Laura , Mancini Antonio , Makhoul Ofa
Published: December 2008

Recent in vitro studies have demonstrated that Ca2+ plays an essential role in gonadotrophin-releasing hormone (GnRH)-stimulated luteinizing hormone (LH) release. In vivo, we have previously shown that verapamil, a substance known to inhibit calcium entry into cells, is capable of inhibiting basal gonadotrophin release as well as the release of luteinizing hormone and follicle-stimulating hormone (FSH) in response to an iv bolus of GnRH. We have examined the effects of calcium antagonists on the two phases of pituitary LH release in response to constant GnRH infusion in normal subjects. In 6 men, constant infusion of GnRH (0.2 μg/min × 4 h) resulted in the expected biphasic LH response, with an initial rapid release of LH during the first hour of infusion, followed by a second phase release during the subsequent 3 h. When verapamil (5 mg/h) was infused together with GnRH over a 4 h period, a significant decline of the rapid as well as delayed release of pituitary LH occurred.

During the calcium antagonist infusion FSH release was also inhibited, indicating that Ca2+ is also important for the release of this hormone.

Our data demonstrate that Ca2+ plays an essential role in the mechanism of GnRH action on both phases of LH release and the release of FSH in normal subjects.
Effect of C-terminal chain shortening on the insulin-antagonistic activity of human growth hormone 177–191
Authors: Wade J. D. , Ng F. M. , Bornstein J. , Pullin C. O. , Pearce J. S.
Published: December 2008

Six synthetic C-terminal shortened fragments of the reduced and S-carbamidomethylated peptide corresponding to residues 177 to 191 of human growth hormone (Cam-hGH 177–191) were assayed for insulin antagonistic activity in vivo. Two of the peptides, CamhGH 177–191 and cam-hGH 177–191 were, in nanomolar quantities, both active in that they caused significant hyperglycaemia and insulin resistance in normal rats. The remaining peptides, hGH 177–180, Cam-hGH 177–185, Cam-hGH 177–187 and hGH 177–189 were all inactive even at up to one hundred times the dose employed for the active peptides. The results indicate that an insulin antagonistic core of hGH is contained within amino acid residues 178 to 190 inclusive.
Thyrotrophin stimulation of adenylate cyclase and iodine uptake in human differentiated thyroid cancer
Authors: Thomas-Morvan Colette , Carayon Pierre , Schlumberger Martin , Vignal Anne , Tubiana Maurice
Published: December 2008

TSH stimulation of adenylate cyclase (AC) and iodine uptake was compared in 39 surgical specimens of primary tumours and/or lymph node metastases from 29 human differentiated thyroid carcinomas.

TSH stimulation of AC was significantly lower (2.1 ± 0.3 fold the basal level) in patients without in vivo 131I uptake than in patients with 131I uptake (4.7 ± 0.8). A significant correlation between TSH responsiveness of AC and TSH stimulation of in vitro 125I uptake was found. There was also a relationship between 127I tissue content and AC responsiveness. Nevertheless analysis of individual data showed discrepancies in about one quarter of the cases. Thus the response of neoplastic cell membrane to TSH appears to be necessary for iodine metabolism, but it is not sufficient. Additional defects may in some cases explain the lack of either iodine uptake or organification. There is a general correlation between TSH stimulation of AC and histological type. However, data from papillary carcinomas with various degrees of uptake capacity show that TSH stimulation of AC correlates better with functional activity than with cell morphology or tissue architecture.

Stimulation by GMP P(N)P was decreased in carcinomas, while NaF stimulation was not significantly different from normal. This suggests that alterations in thyroid cancer are more related to defects in the regulatory than in the catalytic subunit of AC.
Myxoedema and Raynaud's phenomenon
Authors: Nielsen S. L. , Parving H-H. , Hansen J. E. Mølholm
Published: December 2008

Cold hands is a common complaint in myxoedema and were reported by 15 of 17 patients before treatment of myxoedema with 4 having Raynaud's phenomenon. An increased cold sensitivity of the digital arteries could be demonstrated during finger cooling in about half of the patients and Raynaud's phenomenon was verified in the 4 patients as digital arterial closure. The cold sensitivity decreased significantly after treatment with L-thyroxine. The increased cold sensitivity in untreated myxoedema is probably due to an increased sympathetic discharge to the hands that might disclose a predisposition for Raynaud's phenomenon.
The discrepancy between plasma 11-deoxycortisol and ACTH concentrations in a single dose metyrapone test in normal men
Authors: Matsuki Michihiro , Nishida Seikoh , Horino Masaharu , Tenku Atsuko , Oyama Hideki
Published: December 2008

A single dose metyrapone test (MTP test) was carried out on 6 normal men by administering 1.0 g of metyrapone at 08.00–09.00 h with and without dexamethasone (DXM-MTP test) pre-treatment. Plasma 11-deoxycortisol, pregnenolone, ACTH and cortisol were measured before administration of the drug, and at hourly intervals for 6 h. In the MTP test, 11-deoxycortisol increased significantly at 1 h with a peak at 5 h, whereas significant increases in pregnenolone and ACTH were not seen until 3 h. There was a definite decrease in the cortisol level at 1 h with the lowest level measured at 2 h. Thus, a time discrepancy between plasma 11-deoxycortisol and ACTH concentrations was observed. The increase in 11-deoxycortisol after metyrapone should be divided into two phases: the increase in phase II (after 3 h) is due to the pituitary ACTH reserve, and that in phase I (the first 2 h) is due to some mechanism other than the pituitary ACTH reserve. The increased amount of 11-deoxycortisol in phase II (218.1 nmol) occupied 60.5% of the total increased amount in phases I and II(360.6 nmol). The cortisol/(cortisol +11-deoxycortisol) ratio reached its lowest point 3 h after metyrapone treatment. This might be due to the initiation of an additional surge in 11-deoxycortisol by the ACTH reserve at 3 h.
Effect of standard oral glucose loading on aldosterone secretion in primary hyperaldosteronism
Authors: Beretta-Piccoli C. , Weidmann P. , Brown J. J. , Fraser R. , Lever A. F. , Marone C. , Robertson J. I. S.
Published: December 2008

The effects of mild acute decreases in plasma potassium induced by standard oral glucose loading (100 g) on plasma aldosterone and renin levels were assessed in 10 patients with primary hyperaldosteronism as compared with 10 normal subjects. Following overnight fast, mean plasma glucose was identical in both groups; plasma insulin, potassium and renin levels were lower and plasma aldosterone higher in patients than in controls. Glucose loading significantly increased plasma glucose and insulin concentrations and decreased plasma potassium and aldosterone levels in both groups. The increases in plasma insulin and the decreases in plasma potassium or aldosterone tended to be blunted in primary hyperaldosteronism. Glucose-induced changes in plasma aldosterone correlated significantly (P < 0.025) with those in plasma potassium in the patients and with variations in plasma renin activity in the normal subjects. These findings suggest that the metabolic changes induced by glucose ingestion are capable of modifying aldosterone secretion in primary hyperaldosteronism. However, the glucose-induced decreases in plasma aldosterone are blunted in this disorder; this could be related to the impaired insulin response to glucose loading.
Simultaneous measurement of β-endorphin, lipotrophins and met-enkephalin in phaeochromocytomas
Authors: Bertagna X. , Pique L. , Ochoa C. , Luton J. P. , Bricaire H. , Serin D. , Girard F. , Plouin P. F. , Corvol P. , Cesselin F. , Hamon M.
Published: December 2008

Tissue concentrations of immunoreactive lipotrophin, β-endorphin, and met-enkephalin were determined in 10 phaeochromocytomas, 3 of which were responsible for the ectopic ACTH syndrome. Lipotrophin and β-endorphin immunoreactivities could be detected in all cases, whether or not Cushing's syndrome was present, and their tissue concentrations were significantly correlated (r = 0.95, P < 0.001). Chromatographic studies showed tha γ-lipotrophin and β-endorphin were the main peptides in the tumours. Met-enkephalin immunoreactivity was also found in all tumours examined, at much higher concentration and showing no correlation with either lipotrophin or β-endorphin immunoreactivity. Although β-endorphin and met-enkephalin are thought to originate from different precursor molecules, these data show that the two opioid peptides may be secreted by the same tumour. The evidence for excess secretion of opioid peptides and their pathological significance in phaeochromocytomas remain to be established.
Pulsatile low dose luteinizing hormone-releasing hormone treatment for induction of follicular maturation and ovulation in women with amenorrhoea
Authors: Skarin G. , Nillius S. J. , Wide L.
Published: December 2008

Chronic intermittent low dose luteinizing hormone-releasing hormone (LRH) therapy was given to 7 normoprolactinaemic women with long-standing secondary amenorrhoea, low-normal gonadotrophin levels and low endogenous oestrogen production (WHO group I). Four of them were involuntarily infertile. A portable, computerized infusion pump (Zyklomat, Ferring) delivered 20 μg LRH every 90 min through a chronic indwelling catheter inserted sc in the fat tissue of the lower abdominal wall. The LRH administration was continued until menstruation or pregnancy.

Nine treatment courses over 21 to 69 days were given. Twelve ovulatory cycles were induced by the pulsatile LRH treatment. The corpus luteum function was normal in 7 cycles. Temporary interruptions of the pump function in 2 patients and haematomas at the catheter site in another 2 patients may have caused the luteal phase insufficiency. One of the 4 infertile women became pregnant. She developed ovarian hyperstimulation during her first treatment cycle. The ovarian enlargement regressed despite continued LRH therapy and a second ovulatory cycle was induced.

Thus, pulsatile administration of low doses of LRH can induce follicular maturation, ovulation and normal corpus luteum function in hypo- or normogonadotrophic women with secondary amenorrhoea with low endogenous oestrogen production. The LRH therapy can be given with the same pulse frequency throughout the induced cycle. Should pregnancy not occur the pulsatile LRH treatment can be continued without interruption to induce a second ovulatory cycle.