bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanisms of action of testosterone propionate on LH and FSH release by the pituitary gland in cyclic female rats
Authors: Roos J. , Plas-Roser S. , Aron Cl.
Published: December 2008

The aim of this work was to determine whether changes in pituitary responsiveness to LRH could account for the effect of testosterone propionate (TP) on the gonadotrophic function of the pituitary in 4-day cyclic female rats.

Doses of 250, 500 and 1000 ng LRH were injected ip on pro-oestrus at 15.30 h in rats either pre-treated with 5 mg TP on dioestrus II at 10.00 h or injected with 30 mg/kg pentobarbital (PB) at 13.00 h. LH release induced within 30 min by LRH was higher in PB than in TP-treated rats. Even by using 250 ng LRH full ovulation was observed on the morning of oestrus in PB-treated rats. On the other hand, only partial ovulation occurred whatever the dose of LRH used in TP-treated rats; a great number of luteinized follicles was shown to be constantly associated with post-ovulatory corpora lutea. While LRH caused a significant FSH release (30 min later) in TP-treated rats, no FSH release could be shown in PB-treated rats. The pituitary FSH content appeared to be decreased and the pituitary LH content remained unchanged while a sharp increase in both blood FSH and LH concentrations occurred following injection of 1000 ng LRH in TP-treated rats. Concomitantly a sharp decrease in the number of pituitary gonadotrophs (AB-PAS+) was observed. A significant decrease in the number of the small roundshaped PAS positive cells was also observed. The mechanisms whereby TP influences the function of the pituitary-ovarian axis are discussed in the light of these results.
Regulation of serum-progesterone in patients with essential hypertension
Authors: Wambach G. , Koschut M. , Helber A. , Bönner G. , Kaufmann W.
Published: December 2008

Increased levels of progesterone in serum have been reported in male patients with essential hypertension (EH). We, therefore, investigated serum progesterone levels in relation to excretion of aldosterone after 4 days of low Na+ intake and 6 days following high Na+ diets, in 11 normotensive controls, 22 male patients with EH and 8 male patients with hypertension of renal origin (RH). In the group of normotensive controls, the concentration of progesterone in serum averaged 228 ± 90 and 186 ± 93 (mean ± sd) pg/ml during low and high regimens of Na+ intake, respectively, despite a fall in the excretion of aldosterone from 22.8 ± 9 to 1.8 ± 1.4 μg/24 h. Similarly, in patients with EH, serum progesterone remained unchanged during either low or high Na+ intake regimens: 197 ± 73 and 219 ± 83 pg/ ml, respectively. In patients with RH, serum progesterone tended to be lower during both low and high Na+ diets: 167 ± 61 and 185 ± 72 pg/ml, respectively. In 5 normotensive controls, diurnal variations of progesterone and cortisol were significantly correlated (r = 0. 726, P < 0.005).

The results of the present study suggest, that progesterone is not involved in metabolism of Na+, either in normotensive or hypertensive male subjects. Correlation between circadian variations of progesterone and cortisol suggests, that progesterone levels are modified by ACTH secretion.
Biosynthesis and accumulation of cadaverine and putrescine in rat ovary after administration of human chorionic gonadotrophin
Authors: Andersson Anne-Charlotte , Henningsson Stig
Published: December 2008

In the ovaries of pre-pubertal rats stimulated by human chorionic gonadotrophin (hCG) the temporal changes in cadaverine and putrescine formation were investigated. In addition, the dose-response relationship of hCG and its effect on the diamine formation and the effect of hCG on the content of diamines and polyamines in the ovaries and the urine were studied. The results show that the ovary stimulated by hCG, in addition to putrescine, forms cadaverine at a highly increased rate. The elevated diamine formation was parallelled by an increased content of cadaverine and putrescine in the ovary.

Treatment with aminoguanidine elevated the content of cadaverine in the ovary, suggesting that diamine oxidase has a role as a regulator of the intra-ovary level of cadaverine.

These results confirm that cadaverine can be synthesized in an inducible manner in mammalian tissues. This is, virtually, the first report of elevated formation of cadaverine in response to an exogenous gonadotrophin.
Sebum production and plasma testosterone levels in man after high-dose medroxyprogesterone acetate treatment and androgen administration
Authors: Novak E. , Hendrix J. W. , Chen T. T. , Seckman C. E. , Royer G. L. , Pochi P. E.
Published: December 2008

In 47 healthy male volunteers, the administration of 100 mg of oral medroxyprogesterone acetate daily for 42 consecutive days caused a modest 16.7% decrease in sebum production from a baseline mean of 2.28 mg to a post-treatment mean of 1.90 mg. This represented a considerably smaller decrement than had been reported in the literature. Immediately following the period of medroxyprogesterone acetate administration, the addition of daily oral doses of either 50 mg of fluoxymesterone, methyltestosterone, or calusterone to the 100 mg daily dose of medroxyprogesterone acetate for 42 additional days resulted in the return of sebum production to essentially pre-suppression values.

A statistically significant decrease in serum testosterone levels, from a pre-treatment mean of 862 ng/100 ml to a post-treatment mean of 251 ng/100 ml, was seen in all groups treated during the first 42 days with 100 mg of medroxyprogesterone acetate daily (P < 0.05). The addition of 50 mg of fluoxymesterone, methyltestosterone, or calusterone to the 100 mg of medroxyprogesterone acetate for another 42 day period caused a further decrease in serum testosterone levels (P < 0.001); the fluoxymesterone-medroxyprogesterone acetate combination produced the greatest decrease of serum testosterone levels, from a pre-treatment mean value of 932.8 ng/100 ml (Day 1), to a post-treatment mean value of 70.6 ng/100 ml (Day 85).

The daily dose of 20 mg of medroxyprogesterone acetate for 42 consecutive days caused less suppression of serum testosterone levels (from 831 ng/100 ml to a mean of 585 ng/100 ml) than 100 mg of medroxyprogesterone acetate (from 831 ng/100 ml to a mean of 214 ng/100 ml), but more than that of placebo (pre-treatment mean of 886 ng/100 ml to a post-treatment mean of 871 ng/100 ml). Except for changes in haemoglobin, haematocrit and haptoglobin values, no other medically significant changes were seen in the routine screening chemistries and urineanalyses for any of the drug groups. These changes were not unexpected, as they are known to occur with androgen therapy. Of potentially clinical importance was the absence of any effect of antithrombin-3 levels during the study period.

No major side effects were reported other than in one patient who developed gynaecomastia of his right breast on Day 42 of medroxyprogesterone acetate therapy. After his being removed from the study, the gynaecomastia disappeared rapidly.
Extracellular cyclic AMP levels in osteomalacia
Authors: de Castro Jose A. Sisson , Tucci Joseph R.
Published: December 2008

Plasma and urinary cyclic AMP were measured in a 62-year-old man with severe osteomalacia due to a gluten-induced enteropathy. Before therapy, plasma cyclic AMP was normal and both urinary and nephrogenous cyclic AMP were markedly increased. A calcium infusion acutely diminished the elevated iPTH and urinary cyclic AMP levels. Following a bolus infusion of PTE, there was no phosphaturia despite a somewhat exaggerated increase in cyclic AMP excretion. With appropriate therapy, serum calcium, phosphorus, alkaline phosphatase, iPTH and 25-OHD3 and urinary and nephrogenous cyclic AMP gradually returned to normal. The response to PTE infusion after normalization of serum electrolytes, iPTH, and 25-OHD3 levels was similar to that seen before therapy.

These results demonstrate that non-azotaemic malabsorptive osteomalacia is associated with elevations in urinary and nephrogenous cyclic AMP which gradually fall to normal with therapy. In contrast to studies in the vitamin D deficient rat, the maximal urinary cyclic AMP response to PTE is not diminished in the human with malabsorptive osteomalacia. The lack of a phosphaturic response to PTE depite a normal increase in urinary cyclic AMP excretion, as seen in our patient, is similar to that described in some patients with pseudohypoparathyroidism, suggesting that the response is not specific for the latter disorder. Finally, the data suggest that endogenous PTH does not modulate its renal receptors, at least in terms of cyclic AMP generation.
Plasma growth hormone and prolactin responses to TRH and arginine given before and during bromocriptine therapy to patients with acromegaly
Authors: Hanew Kunihiko , Sasaki Atsushi , Mouri Toraichi , Yoshinaga Kaoru
Published: December 2008

The chronic effects of bromocriptine (CB-154) administration on pituitary somatotrophs and lactotrophs were investigated in 9 patients with acromegaly. Following therapy with CB-154 for 3 to 20 weeks, 6 of 9 cases showed a normalization of plasma GH (below 5 ng/ml) and a clinical improvement. These cases were termed 'CB-154-responders'. Plasma GH responses to TRH were observed in all cases of'CB-154-responders' before the therapy and were significantly suppressed during CB-154 therapy, although the response patterns expressed in logarithms were retained. When TRH was administered in 3 cases of acromegaly after acute administration of CB-154 and before chronic CB-154 therapy, the peak plasma GH responses were between those responses seen before and during CB-154 therapy. After iv infusion of arginine, 5 cases of 'CB-154-responders' showed an increase in plasma GH levels. These responses were also significantly suppressed during CB-154 therapy, while the response patterns were also preserved.

In these same patients, basal plasma prolactin was consistently suppressed to low levels (mean ± sem: 3.4 ± 0.9 ng/ml) in all 9 cases during CB-154 therapy and plasma prolactin responses to TRH almost disappeared after either acute or chronic administration of CB-154.

These findings demonstrate: 1) chronic CB-154 therapy in acromegalic patients gradually reduces the activity of the somatotrophs to synthesize and to release GH while it causes a rapid and marked suppression of lactotrophs; 2) the sites of action to CB-154 on the somatotrophs may be different from those to TRH and arginine (possibly GH-RF),while CB-154 and TRH appear to have a close relationship in regard to sites of action on the lactotrophs
Prolactin responses to histamine H2 receptor antagonists
Authors: Sharpe P. C. , Melvin M. A. , Mills Jane G. , Burland W. L. , Groom G. V.
Published: December 2008

We have compared the effects of cimetidine and SK&F 92994, a new more potent histamine H2 receptor antagonist, on serum prolactin, and also assessed the effect of the H2 receptor agonist impromidine on the response to cimetidine. As previously reported, cimetidine 200 mg given as an iv bolus dose produced a marked rise in serum prolactin, but 50 mg and 200 mg of SK&F 92994 given by the same route had no effect. Iv infusion of impromidine 10 μg kg−1h−1 failed to modify the prolactin response to cimetidine. It is concluded that the rise in serum prolactin following iv administration of cimetidine may be due to a specific property of cimetidine. An effect mediated via histaminergic pathways within the central nervous system, although less likely, cannot be excluded.
Effects of glucocorticosteroids on prolactin and growth hormone production and characterization of the intracellular hormone receptors in rat pituitary tumour cells
Authors: Naess Oddvar , Haug Egil , Gautvik Kaare
Published: December 2008

The effect of corticosterone and dexamethasone on the production of growth hormone and prolactin was studied in rat pituitary tumour cells (GH3-cells) in culture. Corticosterone and dexamethasone caused a dose-dependent stimulation of growth hormone synthesis, and the highest concentration (10−6 mol/l) increased growth hormone levels to 250% of controls. This concentration, however, decreased prolactin synthesis to 25% of the control values.

The cytosol fractions from monolayer cultures as well as from tumours of GH3-cells were found to possess receptor molecules for glucocorticoid hormones, having a sedimentation constant close to 8 S in a salt-free buffer and 4 S in the presence of 0.5 mol/l KCL. Isoelectric point of the receptor was 5.8. Scatchard analysis showed one single class of binding sites with high affinity (Kd 2.1 ± 0.4 (sd × 10−9 mol/l). Studies on the steroid specificity revealed that dexamethasone had the highest affinity for the receptor. Corticosterone, cortisol and progesterone had also high affinity, whereas testosterone and oestradiol-17β had no significant affinity for the receptors. After in vivo administration of [3H]dexamethasone to GH3 tumour-bearing rats, radioactivity could be extracted from purified nuclei bound to 4 S macromolecules.

The presence of receptors for glucocorticosteroid hormones in the GH3-cells, suggests that these hormones may alter growth hormone and prolactin production at the anterior pituitary level.
Long-term variability in serum thyroglobulin and thyroid related hormones in healthy subjects
Authors: Feldt-Rasmussen U. , Petersen P. Hyltoft , Blaabjerg O. , Hørder M.
Published: December 2008

From 5 young males and 5 young females blood was drawn under highly standardized conditions at 6 to 10 occasions during 4 months. The serum constituents thyroglobulin, thyroxine, triiodothyronine, T3-uptake test, TBG and TSH were determined, and four indices were calculated.

The biological intra-individual coefficients of variation were below 0.14 for thyroglobulin, and the inter-individual coefficients of variation ranged from zero for T3-uptake test to 0.35 for thyroglobulin.

All results were within the generally accepted reference ranges for normals. Within these ranges the calculations of indices for free thyroxine and triidothyronine according to T3-uptake test and TBG, did not significantly reduce the coefficients of variation for these serum constituents.

Thyroglobulin concentrations did not correlate to any of the measured or calculated constituents. The knowledge of these intra- and inter-individual variations of serum thyroglobulin in healthy persons is of importance for the interpretation of variations found in patients.
Decreased testicular response to acute LH-stimulation and increased intratesticular concentration of oestradiol-17β in the abdominal testes in cryptorchid rats
Authors: Damber Jan-Erik , Bergh Anders
Published: December 2008

Rats were made cryptorchid, bi- or unilaterally, by cutting gubernaculum testis at birth. At 100 days of age the basal plasma testosterone concentration was smaller in bilateral cryptorchid animals as compared to unilateral cryptorchid and control rats. After acute LH-stimulation plasma testosterone concentration increased in all rats, where the highest concentrations were found in the control group. The amount of testosterone in the testis after a 30 min LH-stimulation was lower in both kinds of cryptorchid testes but higher in the scrotal testis of the unilateral cryptorchid rats, all as compared to control testis. This decreased effect of LH observed in cryptorchid animals indicates an impaired Leydig cell function in cryptorchid testis. The results also show a compensatory hyperfunction of Leydig cells in the scrotal testes of unilateral cryptorchid rats. It was also found that the intratesticular concentration of oestradiol-17β was three-fold increased in unilateral cryptorchid testes and even more in bilateral cryptorchid ones.
Pituitary hormone secretion after inhibition of L-aromatic amino acid decarboxylase activity in man
Authors: Delitala G. , Devilla L. , Pende A.
Published: December 2008

The effect of acute administration of 200 mg benserazide, an L-aromatic amino acid decarboxylase inhibitor, on pituitary hormone secretion in humans was studied. Benserazide induced in all subjects a quick and marked increment of serum prolactin (Prl) and TSH levels: at 180 min TSH and Prl levels were still significantly higher than the baseline values. Women with normal menstrual cycles showed a Prl response to benserazide which was significantly greater than that observed in post-menopausal women and men. In another experiment six normal men received 10 mg of domperidone, a peripheral dopamine receptor blocker. The hormonal changes induced by domperidone were comparable to those obtained with benserazide.

Since domperidone and benserazide are thought not to cross the blood-brain barrier, these results suggest that dopamine regulates Prl and TSH secretion through extra blood-brain barrier structures.
Alteration of thyroid function in the early stage of subacute thyroiditis
Authors: Madeddu G. , Langer M. , Costanza C. , Casu A. R. , Arras M. L. , Campus S.
Published: December 2008

Measurement of serum triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), free thyroxine (FT4), thyroxine-binding-globulin (TGB), antithyroglobulin antibodies (anti-hTg), thyroid 131I uptake and scanning was performed on 12 patients during the early phase of subacute thyroiditis. Serum thyrotropin (TSH) was measured during baseline conditions and following administration of synthetic thyrotropin-releasing-hormone (TRH). The stimulation with exogenous TSH was performed on 7 subjects. 131I uptake was depressed in all patients including those with solitary nodules. Free and total hormone concentrations were elevated in the three cases with diffuse gland involvement, whereas an increase of T3 alone was present in 3 patients with unilobar involvement. In the latter group and in the 2 patients with a nodular form T4, FT3 and FT4 levels were within normal limits. Interruption of the pituitary-thyroid feed-back mechanism with absence of thyrotropin response to TRH occurred in 11 patients, independent of whether thyroid hormone concentrations were elevated or normal. In one patient only with unilateral involvement, TSH responsiveness to TRH was normal while 131I uptake was not raised by exogenous TSH, indicating diffuse cellular damage. The normal values of FT3 and FT4 found in patients with normal T3 and T4 levels seem to exclude the possibility that the free hormones are responsible for the interrupted feed-back which represents the main cause of suppressed iodine uptake. However, it is possible that the pituitary-thyroid axis is responding to transient or light increases of free and total T3 and T4 still within their 'normal range'.
Incomplete separation of radioiodinated thyroid hormones in serum using specific antibodies
Authors: Perrild H. , Skovsted L. , Christensen L. Korsgaard
Published: December 2008

Alkaline Sephadex G-25 columns were used to separate labelled 3,5,3',5'-thyroxine, 3,5,3'-triiodothyronine, 3,3',5'-triiodothyronine and 3,3'-diiodothyronine from the serum binding proteins followed by a quantitative elution of each hormone by coupling to its respective antibody. It is shown that although these antibodies (diluted 1:1500–1:100 000) in our radioimmunoassays are highly specific they show a high degree of non-specific binding when they are used in the concentrations necessary to get a maximal recovery of the hormones in column separating experiments.
Effect of neonatal hypothyroidism on maturation of nuclear triiodothyronine (T3) receptors in developing rat brain
Authors: Ishiguro Kazumasa , Suzuki Yukichi , Sato Tamotu
Published: December 2008

Changes of nuclear T3 receptors during brain maturation were studied in normal and hypothyroid rats. In normal rats, the higher receptor concentration present in the neonatal period (0.35 ± 0.04 ng T3/mg DNA) decreased at the age of 14 days (0.25 ± 0.02 ng T3/mg DNA), and remained at this level thereafter to 35 days of age (0.25 ± 0.03 T3/mg DNA). In contrast, hypothyroid rats showed a significantly higher concentration than that found in an age-matched control group at the age of 14 days (0.38 ± 0.07 ng T3/mg DNA), and maintained this level up to 35 days of age (0.37 ± 0.03 T3/mg DNA). The binding affinity was similar in both groups and throughout maturation (mean ± sd in normal groups: 1.9 ± 0.3 × 1010m−1, in hypothyroid groups: 1.7 ± 0.2 × 1010m−1). Plasma T3 concentrations showed changes reciprocal to those in the binding capacity of T3 receptors. These results indicate that nuclear T3 receptors in rat brain mature by the age of 14 days, in association with a decrease in binding capacity, and this process seems to be T3-dependent. The physiological role of the high concentration of T3 receptors observed in neonatal and hypothyroid rat brain during development is at present not clear.
Oestrogen metabolism in adult rat's brain
Authors: Reddy Vangala V. R. , Rajan Renga , Daly Michael J.
Published: December 2008

In vitro incubation of pituitary, hypothalamus and cerebral cortex with [3H]oestrogens revealed that the oestrogens are actively metabolized by these tissues. The covalent binding of oestrone and oestradiol to acid precipitable proteins was observed. Pituitary from male rats exhibited higher covalent binding of oestrogens than females. The 2-hydroxylation was found to be greater than 16-hydroxylation. Furthermore, male pituitary exhibited higher 2-hydroxylation of oestrogens than females. No such sexual dimorphism was observed in 16-hydroxylation. C17-reduction was found to be greater than oxidation in these tissues. Furthermore, the C17-reduction in pituitary and hypothalamus from females was greater than males, which is in contradistinction to protein binding and 2-hydroxylation of oestrogens. In both male and female animals the pituitary was metabolically more active than hypothalamus and cortex. In addition, oestradiol was hydroxylated more than oestrone either at 2- or 16-positions. These results indicate that in central nervous system and pituitary the oestrogens are metabolized preferentially by 2-hydroxylation pathway and it is suggested that the in situ metabolism of oestrogens in neuroendocrine tissues may be important in the control of oestrogen effects on neuroendocrine function and sex behaviour.
Parathyroid hormone response to hypocalcaemia following hypercalcaemia
Authors: Blum J. W. , Kunz P. , Rodriguez S. M. , Fischer J. A.
Published: December 2008

Experiments were designed to study the ability of calcium infusions to suppress parathyroid hormone (PTH) responses to hypocalcaemia, induced by iv infusions of ethylene-glycol-bis(β-aminoethylether)N,N′-tetraacetate (EGTA). When plasma calcium (Ca) was raised for 60 min to levels higher then 2.6 mmol/l, PTH responses to a subsequent fall of Ca due to EGTA infusions for 7 min were significantly reduced (P < 0.02) or abolished when compared to PTH responses during 7-min EGTA infusions in normocalcaemic animals. CaCl2 infusions lasting for 10 min only, however, did not cause a significant reduction of PTH responses to subsequent 7-min EGTA infusions. The results demonstrate, that raised Ca reduced PTH available for immediate release. This effect was time-dependent, since it was only seen, when CaCl2 was infused for more than 10 min prior to the administration of EGTA.
Follicular development in the neonatal mouse ovary; effect of epidermal growth factor
Authors: Lintern-Moore S. , Moore G. P. M. , Panaretto B. A. , Robertson D.
Published: December 2008

The growth of the ovary has been studied in the mouse after administration of epidermal growth factor (EGF). Newborn females injected daily with EGF for the first 5 days of life showed a retardation of ovarian development. The number of follicles in the resting pool (small follicles) was significantly greater than in control animals and there were fewer growing follicles at more advanced stages of development (types 3b and 4). The percentage of mitotic figures in the follicular and surface epithelia of the ovary and the epithelium of the extraovarian rete was also significantly reduced after EGF. The results indicate that EGF may inhibit rather than promote the growth of follicles in the neonatal mouse ovary in vivo.
Influence of sex hormone binding globulin and serum albumin on the conversion of androstenedione to testosterone by human erythrocytes
Authors: Egloff M. , Savouré N. , Tardivel-Lacombe J. , Massart C. , Nicol M. , Degrelle H.
Published: December 2008

The influence of human serum albumin and sex hormone binding globulin (SHBG) on the enzymic conversion of androstenedione to testosterone in human erythrocytes was investigated in vitro. Total plasma and albumin delayed the conversion rate of androstenedione, while SHBG increased it markedly. The effect of SHBG was largely abolished by heating to 60°C for 1 h and by saturating its binding sites by DHT. The effect of both proteins was found to be related to their concentration. It appears that the binding sites of albumin provide a mechanism for retarding androstenedione uptake by the erythrocytes and that the high binding affinity of SHBG for testosterone facilitates the diffusion of this steroid out of the cell and thus, displaces the chemical equilibrium within the cell.
Radioimmunoassay of 6α-methyl-17α-acetoxyprogesterone (MAP) in plasma of sheep during and after oral administration
Authors: Sletholt Kjersti
Published: December 2008

Plasma concentrations of MAP during and after oral administration were measured by a radioimmunoassay technique capable of detecting 2 pg of MAP in 0.1 ml of unextracted plasma. Four ewes were individually subjected to treatment with 50 mg MAP orally per day in 10 days. The maximum plasma concentrations of MAP during the treatment varied considerably among the 4 ewes, the highest recorded was 3.5 ng/ml and the lowest 2.1 ng/ml.

The plasma level of MAP declined to a non-detectable level 5 days after the last administrations in 2 ewes, in the other 2 ewes the level was non-detectable after 6 and 7 days, respectively.
Effect of human growth hormone on the distribution of amino acids between plasma and erythrocytes in pituitary dwarfism
Authors: Uchigata Yasuko , Sato Tamotu
Published: December 2008

To examine the effects of human growth hormone (hGH) on amino acid (AA) transport across the erythrocyte membrane, simultaneous determinations of 14 acidic and neutral AA concentrations in red cells and in plasma, and of gamma-glutamyltranspeptidase (GGTP) activity in red cell membrane were performed in 10 patients with pituitary dwarfism before and/or after hGH therapy. Blood samples were obtained at 0, 1, and 2 h after 4 IU of hGH injection. As AA concentrations in red cells showed wide fluctuations physiologically, samples from 5 normal children at the same intervals served as control. AA distribution was expressed as the concentration ratio of red cell to plasma (R/P). Aspartate and glutamate (group I AAs) showed great intracellular fluctuation concomitantly, which did not appear to be associated with hGH administration. R/P values of most of AAs were significantly decreased in untreated patients (P < 0.01–0.001 vs control), and changes after hGH were very small. In contrast, GH-treated patients exhibited large variance of changes in R/P of threonine, serine, glycine and alanine (group II AAs) at 2 h after hGH loading. However, R/P ratio of cystine, valine, methionine, isoleucine, leucine, tyrosine and phenylalanine (group III AAs) remained low or further depressed by hGH therapy. GGTP activity was also reduced in the untreated patients, while GH-treated patients revealed normal or supranormal GGTP activities. Between GGTP activity and integrated R/P of group II and III AAs, a statistically significant correlation was noted (r = 0.766, P < 0.001). These results suggest that physiologically a dynamic equilibrium exists between AAs in red cells and those in plasma, the transport system of which appears to be different in each group of AAs. hGH seems to exert promoting effects on the shift of AAs across the red cell membrane, at least in part by the activation of gammaglutamyl cycle.
Kinins in relation to renin activity in renal and inferior caval veins in normal individuals and patients with primary aldosteronism
Authors: Hulthén Lennart , Jonsson Kjell , Lecerof Harry , Hökfelt Bernt
Published: December 2008

Blood kinin concentration and plasma renin activity (PRA) were determined in the renal veins and in the inferior caval vein (ICV) below the level of the renal veins in 9 normal individuals (5 men and 4 women) and 7 patients with primary aldosteronism (3 men and 4 women).

PRA in the renal veins and ICV was significantly lower and plasma aldosterone concentration in ICV significantly higher in the patients as compared to the normals. Kinin concentration in the renal veins and ICV did not differ significantly between the patients and the normals (0.31 ± 0.04 (mean ± sem) vs 0.45 ± 0.03 and 0.27 ± 0.05 vs 0.45 ± 0.06 μg/l, respectively).

In the normal individuals kinin concentration and PRA were inversely related in the left renal vein (r = −0.80; P < 0.02), whereas this relation did not reach statistical significance in the right renal vein (r = −0.60; P < 0.10). Kinin concentration in both renal veins was positively correlated to kinin concentration in ICV (r = 0.73; P < 0.05 and r = 0.83; P < 0.02 for the right and left renal vein, respectively).

These results indicate that intrarenal kinin formation and renin release are inversely related in normal subjects. Furthermore, they suggest that one and the same enzyme, possibly renal kallikrein, may be implicated in the kinin formation in the systemic as well as in the renal circulation. Intrarenal kinin formation seems not to be increased in primary aldosteronism.
Urinary excretion of androgen metabolites, comparison with excretion of radioactive metabolites after injection of [4-14C]testosterone. Influence of age
Authors: Deslypere J. P. , Wiers P. W. , Sayed A. , Vermeulen A.
Published: December 2008

The influence of age on the metabolic pattern of [4-14C]testosterone was studied in 20 young and 8 elderly males and compared to the metabolic pattern of endogenous androgens; the latter was also studied in 16 young and 8 elderly women. In both young and elderly males, androsterone and aetiocholanolone glucuronide represent 65% of [4-14C]testosterone metabolites; together with their sulphoconjugates as well as with 5α- and 5β-androstane-3α,17β-diol they represent even more than 75% of total urinary metabolites. The 5α/5β ratio of metabolites of [4-14C]testosterone was significantly (P < 0.01) correlated with the 5α/5β ratio of the metabolites of the endogenous androgens, mainly dehydroepiandrosterone and androstenedione. The 5α/5β ratio of [4-14C]testosterone metabolites was generally higher than the ratio of metabolites of endogenous androgens, suggesting that the transformation of T to ring A saturated metabolites occurs at least partially in another compartment than the transformation of DHEA to these metabolites.

For both [4-14C]testosterone and endogenous androgen metabolites we observed a statistically significant reduction of the 5α/5β ratio with age, a general phenomenon in both males and females. This reduction concerns also 11-OH-androst-4-ene-3,17-dione metabolism. Neither sex hormone levels, nor specific binding seems to determine this age dependent shift; neither is there convincing evidence for latent hypothyroidism or liver dysfunction in the elderly. An age associated primary decrease of the 5α-reductase activity seems the most likely explanation.
Effects of oestradiol benzoate (OeB) and human chorionic gonadotrophin (hCG) on the testes and accessory sex glands of the rat
Authors: Chowdhury Mridula , Tcholakian Robert , Steinberger Emil
Published: December 2008

It has been suggested that treatment of intact male rats with oestradiol benzoate (OeB) causes an interference with testosterone (T) production by the testes by a direct inhibitory effect on steroidogenesis. To test this hypothesis, different doses (5, 10 or 25 IU) of hCG were administered concomitantly with 50 μg of OeB to adult intact or hypophysectomized male rats. The testicular and plasma testosterone, and serum hCG levels were determined. The sex accessory weights were recorded. In the intact OeB-treated group of animals, hCG stimulated both the secondary sex organs and plasma testosterone levels above the intact control group. However, in hypophysectomized animals, although plasma testosterone levels increased above that of intact controls, their secondary sex organ weights did not. Moreover, inspite of high circulating hCG levels, the testicular testosterone content and concentration remained suppressed in OeB-treated animals. The reason for such dichotomy of hCG action on OeB-treated animals is not clear at present.
Dose- and age-dependent effects of clomiphene citrate administered to prepubertal female rats on development of anovulatory sterility and pyosalpinx
Authors: Morishita Hajime , Nakago Kichijiro , Ii Kunio , Hashimoto Tadashi , Mitani Hiroshi , Tomioka Michio , Kuroiwa Shunichiro , Nishiuchi Ken , Okada Akira
Published: December 2008

The influences of dose of clomiphene and age at clomiphene treatment in prepubertal female rats on development of anovulatory sterility and pyosalpinx were investigated. By varying the amount of clomiphene administered, it was found that 50 μg is the minimal dose of clomiphene which will produce anovulatory sterility and pyosalpinx in a majority of female rats treated at 5 days of age. By varying the age of rats at clomiphene treatment, it was observed that the period of clomiphene sensitivity in female rats is within the first 10 days of life, in which administration of 500 μg clomiphene will result in subsequent anovulatory sterility and pyosalpinx. These results demonstrate that the induction of anovulatory sterility and pyosalpinx is dependent upon the dose of clomiphene and the age of rats at clomiphene injection.
An investigation into the origin of the pro-oestrus/oestrus change in pituitary responsiveness to LRH of the pseudopregnant rat
Authors: Schuiling G. A. , Pols-Valkhof N. , Koiter T. R.
Published: December 2008

LH-secretory responses, induced by (standard) infusion of LRH in the pro-oestrous rat, are much greater than in the oestrous rat. In the present investigation the factors which accomplish the transition from the pro-oestrus to the oestrus state of responsiveness to LRH of the pituitary were studied in the pro-oestrous pseudo-pregnant (PSP) rat. It was considered that the change in responsiveness might be caused by either the cyclic release of LRH by the hypothalamus (which results in a depletion of pituitary LH content and an altered state to further stimulation), the peri-ovulatory changes in the endocrine milieu, or some combination of these factors.

It was observed that LH-secretory responses induced 24 h after ovariectomy (OVX) on pro-oestrus, take an intermediate position between the pro-oestrus and the oestrus responses. However, when treated with oestradiol benzoate (OeB), such animals maintain the pro-oestrus state of responsiveness.

Regardless of the presence of OeB or of the ovaries, following the simulation of a 'pre-ovulatory' LH-surge by a 3 h lasting infusion of LRH, the pituitary gland passes into the oestrus state of responsiveness to LRH. When, however, ovulation was induced by hCG, the pituitary passed into the same state of responsiveness as after OVX, i.e. the intermediate position.

It is concluded that the transition from the pro-oestrus to the oestrus state of responsiveness of the pituitary results from the exposure of the gland to the pro-oestrous LRH-surge.
Aldosterone response to sodium deprivation and angiotensin II in patients with hypopituitarism
Authors: Seifert Cornelia , Oelkers Wolfgang
Published: December 2008

Unknown pituitary factor(s) apart from ACTH may participate in the regulation of aldosterone (aldo) secretion in man. We investigated whether the 'sensitization' of the zona glomerulosa against angiotensin II (A II) by sodium deficiency was mediated by the pituitary gland. A II was infused in stepwise increasing doses (2, 4, 8 ng/kg/min) into 5 normal subjects (N) and into 8 patients with hypopituitarism (H) before and after 4 days on a low sodium diet. Mean cumulative sodium balance after the low sodium diet was − 145 mm in N and − 165mm in H. Plasma-aldo and aldo-exretion rate on the normal sodium diet were slightly lower in H than in N but rose less than normal during sodium depletion in H. Plasma A II and renin activity on normal sodium were slightly higher in H than in N, but the increase on the low sodium diet was blunted in H. The stimulation of plasmaaldo by A II infusion was similar in both groups on the normal sodium diet. In both groups, the response of P-aldo to A II infusion was greater in the sodium deplete than in the replete state, although 'sensitization' was slightly less marked in H than in N. This may be due to the blunted rise of plasma-A II after sodium loss in H, which may also account for abnormalities in the blood pressure response in the H group. Altogether, the results speak against a direct involvement of the pituitary gland in 'sensitization', but an indirect influence through unexplained abnormalities in renin secretion is possible.
An autoradiographic study of follicle growth in the ovaries of cyclic rats
Authors: Groen-Klevant A. C.
Published: December 2008

Follicle growth in the ovaries of cyclic rats was studied by autoradiography after pulse labelling with [3H]thymidine: growth rates and numbers were determined for follicles of the types 3b to 6 (type 3b: follicles with 1 –2 layers of granulosa cells; type 6: follicles with a diameter of 200 μm and usually with a single antrum). The data indicate a total time of follicle development, from type 3b to ovulation, of 22 days. Growth of follicles of the types 3b to 6 in these cyclic rats was roughly similar to that in late prepubertal animals, previously studied. However, some changes of the growth of these types of follicles, related to the stages of the cycle, could be noted.
A quantitative test for oestrogenic activity using rat endometrium lactate dehydrogenase
Authors: Jelínková Marta , Jelínek J. , de Visser J. , van der Vies J.
Published: December 2008

In ovariectomized rats treatment with ethinyloestradiol (EOe) po started 1 week after castration and given for 4 days resulted in an increase of endometrial lactate dehydrogenase per DNA (LDH/DNA).

The λ of the dose-response curve was 0.178. In subsequent experiments EOe was used as a standard and the oestrogenic activity of four steroids given po was compared. The effect of testosterone was studied using oestradiol as a standard.

If the activity of EOe is 1, the relative oestrogenic potencies of oestriol succinate, oestradiol decanoate, 11β-methoxymethyl-17α-ethinyl-Δ1,3,5(10)-oestratriene-3,17β-diol and 11β-methoxymethyl-Δ1,3,5(10)-oestratriene-3,16α,17β-triol were 0.074, 0.7, 12.5 and 32, respectively.

The results of the test were compared with the relative potencies of these four compounds in two biological tests, viz. the vaginal cornification in ovariectomized adult rats and stimulation of the uterine growth in immature intact rats. The relative oestrogenic potencies as measured by an increase in the endometrial LDH/DNA were in better agreement with those found in the vaginal cornification assay than with those in the uterine growth stimulation test. Testosterone caused no significant changes of LDH/ DNA. We conclude that the increase in LDH/DNA in the endometrium of ovariectomized rats can be used as a quantitative assay for oestrogenic potency.
Plasma concentrations of progesterone, oestrogens and prostaglandin F in maternal blood and corticosteroids and oestrogens in foetal blood of cows during dexamethasone-induced deliveries
Authors: Fairclough R. J. , Hunter J. T. , Peterson A. J. , Welch R. A. S.
Published: December 2008

Infusing dexamethasone at rates of 0.1, 1.0 or 10 mg/day into 6 foetal calves at day 240 of gestation (2 calves per infusion rate), induced premature calving in a mean 12, 9 and 3 days respectively. Maternal plasma concentrations of progesterone, oestrone, oestradiol- 17β and prostaglandin F or 13, 14-dihydro- 15-keto-prostaglandin F, and foetal plasma concentrations of oestrone, oestradiol-17β and corticosteroids were monitored until calving.

The maternal hormone changes observed for all cows were a decline in progesterone, and a rise in both oestrogen and prostaglandin F concentrations before calving. Dexamethasone infused at a rate of 1.0 and 10.0 mg/day suppressed plasma corticosteroids in the foetus; however at 0.1 mg/day, foetal corticosteroids increased tenfold during the last 3 days before calving. At the lowest rate of infusion, dexamethasone had no effect on foetal oestrogen levels, but at rates of 1.0 and 10.0 mg/day there was a marked rise in foetal plasma levels of oestrogen.
Distribution study of a synthetic ACTH analogue in rat tissue
Authors: Hirata Masaharu , Futaguchi Shinya , Odaguchi Kunihiro , Inouye Ken , Tanaka Akira
Published: December 2008

Tissue distribution of {Aib1, Lys17,18,19}-corticotrophin-(1-19)-nonadecapeptide amide (690024-S), iv injected to hypophysectomized rats, were surveyed by bioassay. Among the tissues examined, the largest amount of 690024-S was found in the liver during 3 h of search for the injection, while a higher concentration of the peptide per tissue weight was found in kidney. Though a small amount of 690024-S was detected in spleen, heart and lung at an early stage, it was not detectable in other tissues such as brain, stomach, small intestine, thigh muscle, fat or foetus. The peptide was found to be excreted into bile for the duration of about 2 h. It was also found that the elimination of 690024-S in blood followed biphasic first order kinetics.
Foetal and maternal plasma adrenaline and noradrenaline concentrations in the late pregnant rat: effects of intra-uterine isotonic saline or uterine handling
Authors: Legrand C. , Maltier J. P.
Published: December 2008

The catecholamines adrenaline (A) and nor-adrenaline (NA) were determined in plasma samples of late pregnant rats and rat foetuses using a radioenzymatic procedure.

In maternal plasma of control rats, values of A were stable during the last three days of gestation (between 5.64 and 6.90 ng/ml) whereas NA values increased just before parturition (+ 70%) and on day 23 post-coitum NA was the main plasma catecholamine.

In foetal plasma of control rats, values of A and NA were constant during the last three days of gestation and A was always higher than NA. For both catecholamines, values in foetal plasma were lower than in maternal plasma.

Blood of rats injected with isotonic saline into the uterus on day 21 of gestation contained 24 h and 48 h later about 2–3 times more A, and no more NA, than blood of control rats.

In foetal plasma the levels of both catecholamines especially of NA were greatly increased after the handling of the uterus or the intra-uterine isotonic saline injection. Both treatments had the same prolonged effect upon A and NA values in foetal plasma. There is no increase of A and NA in maternal and foetal plasma after sham-operation.

Although the values of plasma A and NA were high in control rats because blood sampling was carried out under stressful conditions, these results showed that handling of the uterus or injection of intrauterine isotonic saline was a severe aggression for the mother and foetus.
Rat embryo development in vitro
Authors: Roy S. K. , Sengupta Jayasree , Manchanda S. K.
Published: December 2008

We report the first successful culture of 8-cell/morula stage rat embryos in a fully synthetic medium supplemented with 3% crystalline bovine serum albumin. Eighty-four per cent of morulae developed to blastocysts, showing that this is a highly efficient culture medium for in vitro studies on rat pre-implantation embryos. Blastocyst formation was severely inhibited by antioestrogen (nafoxidine 3 μg/ml) but no further reversal was obtained by giving oestrogen to culture medium containing this antagonist.
Somatomedin A levels in patients with Cushing's disease
Authors: Thorén Marja , Hall Kerstin , Rähn Tiit
Published: December 2008

The serum levels of immunoreactive somatomedin A (SMA) in 23 patients with Cushing's disease, aged 6–61 years, were within the range of healthy subjects for their ages. No correlation was found between SMA and the excretion of cortisol. After im administration of hGH (8 IU = 4 mg) daily for 3 days there was a significant rise in SMA, both determined by radioimmunoassay and radioreceptor assay. Thus no impairment was found in the GH-dependent SMA levels or the ability of hGH to generate somatomedin, which indicates that the growth retarding effect of cortisol is most likely due to a direct effect on the tissue. After treatment with stereotactic radiation to the hypophysis there was a significant decrease in cortisol excretion without any change in SMA levels, indicating the possibility to achieve a selective impairment of the ACTH-cortisol axis.
DDAVP treatment of diabetes insipidus during pregnancy and the post-partum period
Authors: Burrow G. N. , Wassenaar W. , Robertson G. L. , Sehl H.
Published: December 2008

A 23 year old woman with diabetes insipidus who had previously been treated with pitressin, pituitary snuff and chlorpropamide, was treated with DDAVP during pregnancy. DDAVP concentrations immunoassayed as vasopressin were determined in maternal serum and breast milk. Oxytocin antibodies were also determined in maternal serum.
Effect of calcium and potassium on basal and gonadotrophin-releasing hormone (GnRH) stimulated release of luteinizing hormone (LH)
Authors: Zolman Joseph C. , Valenta Lubomir J.
Published: December 2008

LH release from the anterior pituitary was studied by the method of an in vitro superfusion of bovine anterior pituitary tissue slices. LH release was stimulated by increased potassium concentration (23 and 59 mm) and by synthetic GnRH (1 and 4 ng/ml). While the potassium effect was completely dependent on extracellular calcium, that of GnRH was only partially dependent. Additive effect was observed when GnRH followed enhanced potassium infusion but not vice versa. This suggested that the mechanism responding to potassium may be contained within the stimulatory pathway of GnRH. There was a difference in the dynamics of the LH response: maximum response was attained in about 10 min of potassium infusion while infusion of GnRH resulted mostly in multiphasic stepwise release of LH reaching a plateau in 60 to 90 min only. It is speculated that the potassium effect involves the K+, Na+ dependent ATPase.
Triiodothyronine binding to lymphocyte nuclei and plasma cyclic AMP response to intravenous glucagon in patients with peripheral resistance to thyroid hormones
Authors: Elewaut A. , De Baets M. , Vermeulen A.
Published: December 2008

In vitro studies of nuclear binding of triiodothyronine (T3) in lymphocytes were performed in three members of a family with hereditary peripheral resistance to thyroid hormone action. Ficoll-Hypaque® purified lymphocytes were used; the binding characteristics were analyzed by Scatchard's methods.

In 5 euthyroid subjects the apparent mean equilibrium association constant (Ka) was 6.1 × 109 1/mol and the mean maximal binding capacity (Cap) 14.4 × 10−15 mol/ 100 μg DNA. In the 3 members of the family one single set of saturable T3 nuclear binding sites with affinity constants similar to those in the controls (mean Ka = 3.2 × 109 1/mol; mean Cap = 17.4 × 10−15 mol/100 μg DNA) were found.

The glucagon stimulated increase in plasma cyclic AMP was studied in 6 healthy subjects and the four members of the family. The plasma cyclic AMP levels of the patients with hormone resistance were generally within the normal range.

These observations demonstrate that in these patients with peripheral resistance to thyroid hormone binding of T3 to the receptor in the nucleus of lymphocytes is normal; in relation to the high circulating thyroid hormone levels, the thyroid hormone mediated cyclic AMP response is disturbed, suggesting that the defect is at the post-receptor effector level.