bluuebunny/crossref_metadata_2025 huggingface dataset:
Stimulation of the conversion of corticosterone to aldosterone by sodium and water depletion of potassium-deficient rats. Comparison of different experimental procedures
Authors: Haldy Philippe , Müller Jürg
Published: December 2008

Sodium depletion, hypovolaemia or both were induced in potassium-depleted rats by various experimental protocols in order to study mechanisms involved in the regulation of late steps in aldosterone biosynthesis. The relative effects of such manoeuvres upon aldosterone biosynthesis and upon the plasma renin activity were compared. The conversion of corticosterone to aldosterone by incubated adrenal glands could be stimulated by a factor of 3 to 4 within 48 h by each of the following procedures: feeding on a sodium- and potassium-deficient diet or on sucrose, water restriction or treatment with furosemide. A 20-fold stimulation was elicited by experimental oedema due to subcutaneous polyethylene glycol solution or formalin. Intermediate responses were obtained by combining the sodium- and potassium-deficient diet with either water restriction or furosemide treatment as well as by the infusion of angiotensin II. Significant increases in the plasma renin activity, which were however not proportional to the stimulation of aldosterone biosynthesis, were seen in rats kept on the sodium- and potassium-deficient diet or treated by furosemide, polyethylene glycol or formalin, but not in rats kept on sucrose or deprived of water. An elevation in the plasma potassium concentration was observed only in the animals treated with water restriction. These results indicate that during potassium deficiency the stimulation of late steps in aldosterone biosynthesis by sodium and water depletion is mediated by the renin-angiotensin system and by an unknown mechanism which enhances the sensitivity of the zona glomerulosa to angiotensin II. Experimental oedema in potassium-deficient rats seems to be a useful model for further investigations of this mechanism.
Influence of gonadotrophins on cAMP formation in theca cells isolated from pre-ovulatory rat follicles
Authors: Nordenström Knut , Hamberger Lars
Published: December 2008

Pre-ovulatory follicles were obtained from immature PMSG treated rats at various times on the day of pro-oestrus. From these follicles the theca capsules were mechanically isolated and subsequently incubated in the presence or absence of LH and/or FSH. The accumulation of cyclic adenosine 3'5'-monophosphate (cAMP) in tissue plus medium was determined. In certain experiments the rats were injected with LH, FSH or saline 2 h prior to sacrifice.

When the theca cells were isolated from rats sacrificed before the endogenous gonadotrophin surge, FSH added in vitro did not significantly stimulate cAMP formation, while LH had a small but significant stimulatory effect. When isolated 2–5 h after the endogenous gonadotrophin surge the theca cells responded with a marked increase in cAMP formation when exposed to LH in vitro, whereas FSH in vitro still had no stimulatory effect. Theca cells, isolated before the endogenous gonadotrophin surge, from rats pre-treated with a single ip injection of FSH 2 h prior to sacrifice, responded to a subsequent in vitro exposure to LH with a marked increase in cAMP levels.

The results indicate that the FSH component of the endogenous gonadotrophin surge increases the sensitivity of the theca cells to LH - i.e. in vivo exposure to FSH seems to be essential for the development of responsiveness of the cAMP system to LH in the theca cells from pre-ovulatory rat follicles.
Indirect evidence of chronic Leydig cell desensitization in Klinefelter's syndrome
Authors: Smals Anthony G. , Pieters Gerlach F. , Kloppenborg Peter W.
Published: December 2008

The basal plasma 17α-hydroxyprogesterone (17-OHP) and testosterone (T) levels were proportionally decreased in 10 hypergonadotropic patients with Klinefelter's syndrome. The ratio 17-OHP to T was however about twice as high as in 10 eugonadal male controls, suggesting the presence of a block in the conversion of 17-hydroxylated steroids to androgens in the Klinefelter patients under basal circumstances. Administration of human chorionic gonadotrophin (hCG, 1500 IU im daily for 3 days) to the Klinefelter patients disclosed a response pattern quite different from that observed in controls. In the control subjects 17-OHP and the ratio 17-OHP/T sharply rose to maximum values at 24 h after the first injection. Thereafter both progressively fell to lowest values at 72 h, when T levels reached their maximum. In the Klinefelter patients the T response to hCG administration was greatly diminished but the 17-OHP response was similar to that in the controls. Maximum 17-OHP and 17-OHP/T values however were not achieved until 72 h after the first injection when T levels also reached their maximum. Unlike in the controls in the Klinefelter patients maximum 17-OHP and T increments and the 17-OHP and T levels 48 and 72 h after the injection were positively correlated.

Together the findings of a decreased T synthesis and reserve in the presence of relative 17-OHP accumulation, further increasing after acute hCG administration in a pattern quite different from that in normal men, suggest that in Klinefelter's syndrome the Leydig cells may be chronically desensitized by the persistent endogenous hypergonadotropism.
Effects of two histamine H2-receptor blocking drugs on basal levels of gonadotrophins, prolactin, testosterone and oestradiol-17β during treatment of duodenal ulcer in male patients
Authors: Peden N. R. , Boyd E. J. S. , Browning Margaret C. K. , Saunders J. H. B. , Wormsley K. G.
Published: December 2008

In a study of 51 male patients with duodenal ulcer, treatment with cimetidine was accompanied by an increase in basal levels of serum testosterone. Treatment with ranitidine, a new histamine H2-receptor antagonist, produced no such effect. It is concluded that cimetidine has antiandrogenic activity in man which is separate from the histamine H2-receptor blocking activity.
Age-related changes in [125I]hLH specific binding to rat interstitial cells
Authors: Clausen O. P. F. , Purvis K. , Hansson V.
Published: December 2008

Enriched Leydig cell suspensions were prepared from rats ranging from 5 to 80 days of age. The cells were incubated with [125I]hLH in vitro, and the proportion of LH binding cells determined by means of autoradiography. The proportion of 3β-hydroxy-steroid-dehydrogenase (3β-HSD) positive cells was also determined. By means of Scatchard analysis and determination of grain counts of LH positive cells, an increase in LH receptors per LH binding cells with increasing age was found. LH binding cells from animals 5 and 10 days of age had few LH receptors, more than a doubling occurred between day 10 and day 20, a significant increase was seen between day 20 and 40 whereas only a slight increase in LH receptors per LH binding cell was seen thereafter. Scatchard analysis and grain count analysis of labelled cells gave essentially the same results. The grain count distribution showed cells distributed around low grain values in animals of all ages, whereas a subpopulation of cells with high grain counts appeared in maturing and mature animals. Only a small fraction of LH positive cells had detectable levels of 3β-HSD activity in animals 5 and 10 days of age. With increasing age the proportion of 3β-HSD positive cells approached that of LH binding cells, indicating that rat interstitial cells aquire LH receptors well before any 3β-HSD activity can be traced.
Short- and long-term fluctuations in plasma prolactin concentration in normal subjects
Authors: Djursing Henning , Hagen Claus , Møller Jan , Christiansen Claus
Published: December 2008

The physiological changes in plasma prolactin concentration were studied in 447 normal subjects, including 65 men, 75 pre-menopausal women and 307 post-menopausal women. The within-day and day-to-day variation as well as the circadian and circannual rhythm of plasma prolactin levels were determined. Furthermore, the relationship between changes in prolactin and oestradiol-17β levels during the normal menstrual cycle and in the climacteric was studied.

Pre-menopausal women had significantly (P<0.01) higher basal plasma prolactin concentration than men and post-menopausal women. Furthermore, they had significantly (P < 0.01) higher day-to-day variation than men. This suggests that prolactin in women is secreted in a pulsatile fashion. Only small seasonal variations in both sexes were seen.

The levels of plasma prolactin during the ovulatory and the luteal phase in the cycle were significantly (P < 0.02) higher than that of the follicular phase, and a positive correlation between changes in plasma concentration of oestradiol-17β and prolactin was found. Also in post-menopausal women a relationship between plasma concentration of prolactin and oestradiol-17β was seen.

It is concluded that the assessment of prolactin concentration in blood is dependent on the physiological variation recorded during sleep in both sexes. However, only in women day-to-day changes and the changes related to the menstrual cycle and the climacteric are of importance.
Existence of multiple molecular forms of luteinizing hormone in rat: differences in immunological and biological activities between stored and circulating forms
Authors: Reddy P. V. , Menon K. M. J.
Published: December 2008

LH from rat anterior pituitary and serum was characterized with respect to its molecular size, and immunological and biological activity. Pituitary extracts prepared by homogenization followed by high speed centrifugation and chromatography on Ultrogel (AcA 44, 1.5 × 80 cm) columns showed two peaks of radioimmunoassayable lutropin (LH) activity, a major peak 1 and a minor peak 2. On the basis of their elution from Ultrogel columns, peak 1 had a larger molecular size (Kav = 0.44) than peak 2 (Kav = 0.53). The biological activities of the two peaks were assessed by testing the ability of the two peaks to stimulate cAMP production and progesterone synthesis using immature rat ovarian cells. Both cAMP production and progesterone synthesis by ovarian cells were stimulated by peak 1 and peak 2 in a dose dependent manner, but differed in the degree of stimulation. At optimal concentrations, stimulation of cAMP production by peak 2 was 1.45-fold higher than peak 1. Similarly, stimulation of progesterone production by peak 2 was 2-fold higher than that produced by peak 1. The molecular size of the LH released from anterior hemipituitaries in response to a gonadoliberin (LRH) agonist, [Des-gly-NH210]LRH ethylaminde, was also determined. Chromatography of control medium as well as the agonist treated medium on the Ultrogel columns showed a single peak of LH activity at a position which corresponded to peak 1 found in the pituitary extract. However, the elution profile of serum LH from animals injected with LRH agonist was found to be similar to that of peak 2 of the pituitary extract. Incubation of the pituitary extract with serum resulted in a shift in the position of elution of peak 1 towards peak 2. From these studies it is concluded that the anterior pituitary contains a major high mol wt form of LH with lower biological activity and a minor low mol wt form with higher biological activity, but only the low mol wt form appears in the circulation.
Oestrogen-like effects of tamoxifen on the concentration of proteins in plasma
Authors: Fex Göran , Adielsson Göran , Mattson Willy
Published: December 2008

The concentrations of 11 plasma proteins were determined by electroimmunoassay in 6 female and one male patient before and after treatment for 1–4 months with tamoxifen (30 mg/day) for advanced cancer. The concentrations of transcortin, sex hormone binding globulin, pregnancy zone protein, apolipoprotein AI and thyroxine binding globulin increased significantly. The concentrations of orosomucoid and haptoglobin decreased significantly. The concentrations of albumin, transferrin, prealbumin and retinol-binding protein showed no significant change. The changes after treatment with tamoxifen were thus similar to those which occur after the administration of oestrogens or during pregnancy although they were quantitatively less pronounced. There were also differences in the pattern of change between treatment with tamoxifen and during pregnancy. There was no apparent relationship between response to treatment and changes in concentration of plasma proteins.
A model for studies on the response of the ventral prostate to oestrogens
Authors: Corrales J. J. , Høisaeter P. A. , Kadohama N. , Murphy G. P. , Sandberg A. A.
Published: December 2008

The effects of oestrogen administration on the weight of ventral and dorsolateral prostates were studied in castrated rats of Wistar-Furth and Copenhagen strains. Direct effect of oestradiol (Oe2) on prostatic tissue was also investigated in organ culture. Oe2-treated animals received daily injections of 50 μg for 7 days. Control animals were treated with the vehicle only (peanut oil). In 4 month old Copenhagen rats the mean weight of the ventral prostates (42.4 ± 9.4 mg/100 g body weight) was significantly higher than that in the control animals (19.9 ± 4.6 mg/100 g body weight, P < 0.0001). No such differences were observed in older Copenhagen rats (9 months old) or Wistar-Furth rats (3 and 6 months old). Thus, this effect of Oe2 on ventral prostate seems both strain specific and age specific. Similar strain and age differences in the Oe2 effect were found in the dorsolateral prostate, but to a smaller extent. Direct interaction of Oe2 with target tissue was demonstrated in culture as evidenced by the ability of the steroid to prevent regression in explants derived from prostates of Copenhagen rats.

The in vivo effects of Oe2 on the prostate weights could not be explained by differences in specific androgen or oestrogen receptor contents or in testosterone (T) metabolism. However, the prostates of younger Copenhagen rats differed from those of all other groups in three respects: 1) they contained high levels of oestramustine binding protein (OeBP), 2) they had the highest amount of uptake of radioactivity into the nuclear residue, and 3) their histological picture was characterized by diffuse stromal architecture having the appearance of oedematous tissue.
Effects of water deprivation on immunoreactive angiotensin II levels in plasma, cerebroventricular perfusate and hypothalamus of the rat
Authors: Yamaguchi K.
Published: December 2008

To examine whether endogenous angiotensin — which has been suggested to produce increased vasopressin (ADH) release and water intake under dehydration, by stimulating the central nervous system — is derived from the brain or from the circulating blood or from both, the effects of water deprivation for 46 h on immunoreactive angiotensin II (AII) concentrations of plasma, cerebroventricular perfusate and the hypothalamus were studied in conscious and urethane-anaesthetized rats. Immunoreactive AII in plasma and the hypothalamus was extracted with acetone and petroleum ether preceding the determination by radioimmunoassay. The water deprivation significantly increased plasma immunoreactive AII concentration (P < 0.002) together with plasma osmolality and sodium concentration, and reduced the potassium concentration. However, neither the immunoreactive AII concentration of the ventricular perfusate nor that of the hypothalamus was affected. Both the perfusate and the hypothalamus were very poor in immunoreactive AII (< 35.0 pg/ml and < 46.7 pg/g wet tissue, respectively). These results may suggest that increased ADH release and water intake under dehydration are brought about by the angiotensin formed in the circulating blood rather than in the brain.
Further evidence of the dual role of noradrenaline in regulation of thyrotrophin secretion in male rats
Authors: Männistö P. T. , Mattila J. , Tuomisto J.
Published: December 2008

The dual role previously suggested for noradrenergic neurons in TRH-TSH regulation was studied in male rats. α-Methyl-p-tyrosine (αMPT) significantly decreased brain noradrenaline (NA) and dopamine (DA) levels 0.5–6 h after the injection. Maximum inhibition of TSH cold-response occurred at 4 h. One h after administration of l-dopa the brain DA (but not NA) level was considerably elevated. TSH cold-response was not significantly changed. The effects of αMPT and Ca-fusarate on the cold-induced TSH secretion were antagonized by neither dihydroxyphenylserine (DOPS; this drug restores NA stores) nor by l-dopa (which restores DA levels). DOPS even potentiated the depressive effect of αMPT and Ca-fusarate. When given into the third ventricle, NA did not modify basal TSH levels but decreased the cold-induced TSH secretion. When infused directly into the median eminence of the medial basal hypothalamus, NA reduced both basal and cold-induced TSH secretion. Pinealectomy decreased the TSH cold-response but NA seemed to retain its ability to inhibit TSH secretion. These results demonstrate that besides the possible stimulatory action on TSH secretion, noradrenergic neurons also have an inhibitory effect outside the blood-brain barrier, possibly in the median eminence.
Stimulation by serum of aldosterone production from rat adrenal glomerulosa cells in vitro: relationships to K+, serotonin and angiotensin II
Authors: Mendelsohn F. A. O. , Kachel Christine D.
Published: December 2008

Normal human serum markedly stimulated aldosterone production from rat adrenal glomerulosa cells incubated in Krebs Ringer bicarbonate medium (KRBGA). The effect was dose-related. In [K+] 3.6 mm KRBGA medium, serum stimulated aldosterone output to higher levels than those produced by maximal doses of serotonin (5 HT), angiotensin II (AII) or high [K+] (8.4 mm).

Cells maximally stimulated by high [K+], 5 HT or AII in KRBGA medium were further stimulated by serum. The angiotensin analogue, [Sar1, Ala8]-AII abolished the effect of AII but not that of high [K+] or serum.

Basal and ACTH-stimulated corticosterone outputs of rat fasciculata cells were not significantly affected by sera known to stimulate glomerulosa cells.

Aldosterone stimulating activity of serum was dialysable and fully recovered in a serum ultrafiltrate.

The serotonin blockers methysergide and metergoline abolished the aldosterone stimulating activity of serum but also depressed basal aldosterone output and methysergide reduced K+-stimulated output.

Chymotrypsin digestion abolished the aldosterone stimulating activity of AII but not that of serotonin or serum.

5 HT concentration of sera was measured and found to be near the threshold for aldosterone stimulation.

Sodium loading and depletion of 4 normal subjects did not consistently modify the aldosterone stimulating activity of their sera.

In a supplemented medium (RPMI 1640), basal and K+-stimulated aldosterone outputs were higher than in KRBGA medium. Under these conditions serum stimulated aldosterone output in normal [K+] medium but only marginally in high [K+] medium. In RPMI medium, serum did not further stimulate cells maximally stimulated with serotonin.

Serum appears to stimulate aldosterone production from glomerulsoa cells by two different mechanisms: One is probably due to a serotonin-like substance. A separate effect of serum, seen only in KRBGA medium, is to enhance aldosterone output of glomerulosa cells maximally stimulated by K+, 5 HT or AII.
Effects of 22S-hydroxy-cholesterol and other hydroxylated sterols on the ACTH-stimulated steroid production in rat adrenal cells
Authors: Huijmans J. G. M. , Degenhart H. J. , Kortleve D. J. , Visser H. K. A.
Published: December 2008

Several effects of hydroxylated sterols on cell cultures are known. Most of these can be explained by an inhibition of the cholesterol synthesis at the level of the 3-hydroxy-3-methylglutaryl CoA reductase.

When studying cholesterol metabolism in rat adrenal cells, an inhibitory action of some sterols on the ACTH-stimulated corticosterone production was observed. The effects of one sterol, 22S-OH-cholesterol, were investigated further.

The sterol had no effect on the ACTH-stimulated cyclic AMP production, suggesting an intact receptor-adenylate cyclase complex and cellular membrane. In the presence of ACTH and 22S-OH-cholesterol particularly the free cholesterol concentration was elevated; 22S-OH-cholesterol therefore probably exerts its inhibitory effect at a step located after hydrolysis of the cholesterol esters. 22S-OH-cholesterol had no effect on the conversion of exogenous pregnenolone into corticosterone.

These results make it probable, that the inhibitory effect of 22S-OH-cholesterol on the ACTH-stimulated corticosterone production is situated at the level of the cholesterol side-chain cleavage.
Delayed stimulatory effect of cyclic AMP on bone resorption in vitro
Authors: Lerner Ulf , Gustafson Gunnar T.
Published: December 2008

The effect of dibutyryl cyclic AMP (dbcAMP) and the phosphodiesterase inhibitors 3-isobutyl methylxanthine (IBMX) and theophylline on bone resorption was studied in an organ culture system for 96– 144 h using half calvaria from 6–7 day old mice. The magnitude of resorption was assessed by measuring the release from the bones of previously incorporated 45Ca. It was observed that dbcAMP, IBMX and theophylline, following a lag period or a period of reduced bone resorption, all progressively increased mineral mobilization. Although the continuous presence of dbcAMP increased mineral mobilization more than a temporary exposure, a limited treatment of 24 h with the nucleotide was sufficient to bring about the delayed stimulatory response. It is concluded that the observations support our earlier proposal that cAMP is not a mediator of the early stages of parathyroid hormone (PTH)- and prostaglandin E2 (PGE2)-stimulated bone resorption. We suggest that the role played by cAMP may be related to the capacity of PTH and PGE2 to develop new osteoclasts, a phenomenon which takes more than 24 h to be observed.
Dopaminergic and adrenergic effects on plasma LH levels in rats with hypothalamic islands
Authors: van Dieten J. A. M.J. , van Valkenburg C. F. M. , de Koning J. , van Rees G. P.
Published: December 2008

In female rats hypothalamic islands were prepared by making a cut around the mediobasal hypothalamus. Three weeks later the rats were ovariectomized. Two weeks after ovariectomy, part of the animals showed elevated blood LH levels with oscillations, although the mean LH levels were significantly lower than in sham-operated ovariectomized animals. There was a significant correlation between the occurrence of elevated blood LH levels after ovariectomy and the inclusion of at least part of the suprachiasmatic nucleus within the islands. Noradrenaline content of the hypothalamus was decreased significantly, but there was no significant change in hypothalamic dopamine content. Injection of doses of apomorphine, ranging from 2.5 μg/kg to 25 mg/kg sc into island-bearing and sham-operated animals caused a dose-dependent decrease of plasma LH. However, the magnitude of the decrease was smaller in rats with hypothalamic islands than in controls. Even the highest doses of apomorphine did not decrease plasma LH further than to about 100 ng of LH-RP-1/ml. Phenoxybenzamine (10 and 40 mg/kg ip) and phentolamine (20 mg/kg ip) caused a decrease of plasma LH in ovariectomized control rats, but in ovariectomized rats with hypothalamic islands these drugs caused an increase. Clonidine (100 μg/kg sc followed by 100 μg/kg ip) had no effect in ovariectomized control rats, but in ovariectomized rats with a hypothalamic island an increase was induced. These results may have been caused by an increased sensitivity of hypothalamic α-receptors resulting from severing afferent noradrenergic fibres.
Beta-adrenergic stimulation of the release of ACTH- and LPH-related peptides from the pars intermedia of the rat pituitary gland
Authors: Tilders F.J. H. , Post M. , Jackson S. , Lowry P.J. , Smelik P. G.
Published: December 2008

The intermediate lobe of the rat pituitary gland produces a series of peptides related to ACTH and LPH. The spontaneous and isoproterenol-stimulated release of such peptides was studied during in vitro superfusion of rat neurointermediate lobes with Krebs-Ringer medium. Products released into the superfusion medium were quantified by direct measurement or after chromatography on Sephadex G-50. ACTH bioactivity was determined by use of adrenal cortical cell suspension assay. In addition, NH2-terminal ACTH, CO2H-terminal ACTH, α-MSH and β-endorphin radioimmunoassays were used. The results show that

1. neurointermediate lobes of rats secrete spontaneously various ACTH- and LPH-related peptides in amounts proportional to the amounts in which these peptides are found in extracts of the neurointermediate lobe;

2. the β-adrenergic agonist, isoproterenol, stimulated the spontaneous release of various peptides, including α-MSH, ACTH, CLIP, glycosylated CLIP, and β-endorphin-like peptides;

3. isoproterenol induced a dose-dependent (10−9–10−7 m), parallel increase in the release of α-MSH and ACTH following similar time courses and showing indentical EC50 values (about 10−8 m).

Although the spontaneous release of α-MSH and ACTH from rat neurointermediate lobes is not strictly coupled under the conditions used in this study, isoproterenol seems to affect the spontaneous release of these peptides to the same relative extent.
Effect of dietary calcium on secretion of calcitonin and gastrin in rats with medullary thyroid carcinoma
Authors: Hongslo Cecilie F. , Myhre Lisbeth , Flaten Olav , Johannessen Jan W. , Gautvik Kaare M. , Ekeland Arne
Published: December 2008

Rats transplanted with medullary thyroid carcinoma (MTC) were divided into 3 groups which received for 34 weeks diets with low (0.09%), medium (0.40%) or high (1.80%) calcium content with a calcium/phosphate ratio 2:1. After 6 weeks the different calcium regimens produced corresponding variations in serum calcium and inverse changes in serum magnesium. No alterations in serum proteins were observed.

Serum immunoreactive calcitonin (iCT) was unaltered until week 28 of the experiment, but thereafter increased rapidly by about 4-fold. No difference in serum iCT was observed between the 3 groups at any time. Immunoreactive serum gastrin was reduced in rats on medium and low calcium diet compared to those on a high calcium diet. After 28 weeks, when serum iCT was rising, gastrin values fell in rats on high calcium diet to levels approaching those in the other groups. With increased serum iCT (weeks 28–34) serum gastrin concentrations were low and equal in the 3 groups despite different serum calcium concentrations. Electronmicroscopic examination of tumours from the various diet groups did not reveal significant ultrastructural differences.

In conclusion: low, medium and high calcium intake gave corresponding changes in serum calcium. Diet-induced hypercalcaemia was not normalized by elevated serum iCT. In contrast, serum immunoreactive gastrin maintained by high calcium diet was suppressed by hypercalcitoninaemia.
Immunohistological demonstration of ACTH-like immunoreactivity in the foetal adrenal medulla in the 23rd week of gestation
Authors: Ito Seiki , Iwanaga Toshihiko , Yamada Yukio , Suzuki Toshimitsu , Sudo Norihito , Momotsu Takeshi , Shibata Akira
Published: December 2008

By an indirect immunofluorescence technique and silver impregnation, cells reacting with anti-1-18ACTH antiserum were demonstrated in the foetal adrenal medulla only in the 23rd week of gestation. They were not found in the foetal adrenal glands before the 23rd week or after 29th week and after birth. The result was confirmed by immunohistological examination using anti-1-18ACTH rabbit IgG purified by affinity chromatography. No cells in the foetal adrenal medulla in the 23rd week of gestation were stained positively by using anti-β-MSH and anti-β-endorphin antisera. This finding suggested, therefore, that the synthetic mechanism of ACTH-like immunoreacticvity in the foetal adrenal glands was different from that in the pituitary. In view of the findings that some phaeochromocytoma contained ACTH-like immunoreactivity, the present study suggested that the origin of the phaeochromocytoma containing ACTH-like immunoreactivity may be the cells of the foetal adrenal medulla in about the 23rd week of gestation.
The endocrinology of testicular germinal cell tumours
Authors: Aiginger P. , Kolbe H. , Kühböck J. , Spona J. , Geyer G.
Published: December 2008

Oestradiol (Oe2), testosterone (T), luteinizing hormone (LH), follicle stimulating hormone (FSH), β-human chorionic gonadotrophin (β-hCG) and alpha-l foetoprotein (AFP) were measured in blood samples taken from 63 patients with testicular tumours. In patients without tumour recurrence (n = 31) AFP, Oe2 and T were within the normal range, β-hCG was negative, LH levels were marginally elevated and FSH concentrations were significantly elevated. In patients with tumour recurrence (n = 32) Oe2 was significantly elevated, whereas the T levels varied considerably and were therefore statistically not different from the patients without tumour recurrence. The β-hCG positive subgroup of the recurrence group, however, demonstrated significantly elevated T levels. T levels were highest in patients with 51 to 500 U β-hCG/l. On the other hand T was normal or even low normal in β-hCG negative-AFP positive patients. In all subgroups decreasing FSH levels and decreasing LH responses to LRH were among the earliest signs of tumour recurrence.

The observations suggest that moderate hCG levels are able to stimulate testicular T production, whereas high levels no longer increase T serum concentrations. Increased conversion rates from steroid precursors to oestradiol seem to be a feature of β-hCG positive as well as β-hCG negative testicular tumours.
Mechanism of creatinuria in experimental hyperthyroidism
Authors: Carter Willam J. , Benjamin Wieke S. van der Weijden , Faas Fred H.
Published: December 2008

Using rats pre-labelled by [14C]creatine injection, the mechanism of creatinuria induced by experimental hyperthyroidism during a 20 day treatment period has been examined. The excess creatine excretion is the result of increased release of creatine from muscle and increased excretion of creatine synthesized de novo. The increased excretion of newly synthesized creatine in hyperthyroidism appears to occur because of decreased creatine uptake by muscle, an increased rate of creatine synthesis, or a combination of both factors. The radioactive creatine content of hyperthyroid skeletal muscle was reduced at the time of death indicating an increased rated of creatine loss during the treatment period. In spite of the increased loss of labelled creatine, the specific activity of creatine obtained from hyperthyroid skeletal muscle was higher than control. This finding is probably due to decreased uptake of unlabelled creatine by hyperthyroid skeletal muscle during the treatment period. In contrast to skeletal muscle, the radioactive creatine content of hyperthyroid myocardium was higher than control at the time of death suggesting a decreased rate of creatine loss during the treatment period.
Plasma insulin, C-peptide, and blood glucose in portal, hepatic and peripheral veins in liver cirrhosis. Effect of intravenous tolbutamide
Authors: Pelkonen R. , Kallio H. , Suoranta H. , Karonen S.-L.
Published: December 2008

The responses of portal, hepatic and peripheral venous blood glucose (BG), plasma insulin (IRI) and C-peptide (IRC) levels to iv tolbutamide (200 mg) have been determined in 9 non-diabetic patients with liver cirrhosis and in 6 control subjects. The basal levels of plasma IRI and IRC were similar in patients and controls as were the portal and peripheral BG levels. In the hepatic vein, however, the BG-levels were higher in cirrhotic patients than in controls. After tolbutamide administration the BG-levels were unchanged in the cirrhotic patients but a significant fall in hepatic vein BG was observed in controls. In both groups of subjects the highest post-tolbutamide IRI-levels were found in the portal vein whereas the corresponding IRC-levels were as high in the hepatic as in the portal vein. The increments of portal venous IRI and IRC were signifiantly higher in controls as compared to the cirrhotic patients. Nevertheless, in the peripheral veins the increments of IRI and IRC were very similar in both groups of subjects or even less in the control subjects.

The results suggest that in patient with liver cirrhosis the secretion of insulin is not increased but slightly decreased. The production of glucose by the liver also seems to be increased either due to insulin resistance or portal venous shunting of insulin.
Insulin secretory response to different secretagogues in hyper- and hypothyroid mice
Authors: Ahrén Bo , Lundquist Ingmar
Published: December 2008

The influence of long-term changes in thyroid state on insulin secretion was investigated in vivo in mice. Hyperthyroidism was induced by daily injections of i.-triiodothyronine and hypothyroidism by a single injection of 131I. Four different insulin secretagogues were used to characterize the insulin secretory response, i.e. glucose, the β2-adrenoceptor agonist terbutaline, the cholinergic agonist carbachol and the synthetic C-terminal octapeptide of cholecystokinin, CCK-8.

In the hyperthyroid mice the plasma glucose level was moderately decreased. Despite this lower glucose level the insulin response to terbutaline and glucose were potentiated by about 200%. Insulin response to CCK-8 and carbachol was less enhanced, by about 100 and 50%, respectively. Liver and muscle glycogen levels were markedly reduced.

The hypothyroid animals showed reduced insulin responses to all secretagogues; after terbutaline by 100%, after carbachol by 70%, after glucose and CCK-8 by 50%. Plasma glucose and muscle glycogen levels were normal, whereas liver glycogen levels were moderately enchanced.

Insulin release induced by β-adrenoceptor stimulation was most markedly affected by the thyroid state, which thus may be of importance for the balance between the β- and α-adrenoceptors of the insulin cell. Since thyroid activity influenced the insulin response to all secretagogues it cannot be excluded that the thyroid state also exerts effects not related to the adrenoceptors.
Characterization of triton-solubilized TSH receptors from human thyroid plasma membranes
Authors: Iida Yasuhiro , Konishi Junji , Kasagi Kanji , Ikekubo Katsuji , Kuma Kanji , Torizuka Kanji
Published: December 2008

The TSH receptor from human thyroid plasma membranes has been solubilized in 10 mm Tris/HCl, 50 mm NaCl, pH 7.4 containing 0.5% triton X-100. Binding of [125I]TSH to the soluble receptor showed rapid and reversible kinetics and reached a maximum within 30 min at 37°C, by 1 h at 25°C and by 24 h at 4°C. Optimal pH was 7.4. The soluble receptor retained specificity with cross-reactivity only to crude hCG (0.03%). Scatchard plots were curvilinear, indicating the presence of at least two binding sites. The high affinity site showed an affinity constant of 1.1 × 109 m−1 with binding capacity of 1.3 × 10−10 m/mg protein. TSH-binding inhibitor immunoglobulins from patients with Graves' disease inhibited [125I]TSH binding to the soluble receptor in a dose-dependent manner. NaCl inhibited the TSH binding and this was ascribed to the decrease in the receptor capacity. Trypsin, neuraminidase and phospholipase C treatment of the solubilized receptor had no effect on TSH binding. The apparent molecular weight of the receptor, determined by gel filtration on Sepharose® 6B, was approximately 300 000.
A possible role of arginase in the regulation of polyamine biosynthesis in the rat thyroid
Authors: Matsuzaki Shigeru , Suzuki Mitsuo , Hamana Koei
Published: December 2008

Effect of chronic methylthiouracil (MTU) treatment on the thyroid arginase activity and thyroidal concentration of arginine, ornithine and other amino acids was studied in the rat. The activity of thyroid arginase increased significantly at 15 days of MTU treatment and the elevated enzyme activity was reduced to normal by l-thyroxine (T4) injection. The thyroidal concentration of polyamines was increased by MTU and decreased by T4 with the exception of spermine. The thyroidal concentration of arginine and lysine, a substrate and an inhibitor for arginase respectively decreased significantly, while that of ornithine remained unchanged after MTU treatment. T4 injected to MTU-pretreated rats restored the decreased arginine concentration to normal. These results suggest that ornithine supply for polyamine biosynthesis is regulated by the level of both arginase and lysine in the thyroid.
Changes in the cyclic nucleotides (cCMP, cAMP and cGMP) of rat thyroid induced by prolonged administration of LATS and TSH
Authors: Ochi Yukio , Hosoda Shiro , Hachiya Takashi , Yoshimura Manabu , Miyazaki Tadayoshi , Kajita Yoshihiro
Published: December 2008

It has recently been suggested that cyclic CMP (cCMP) has a physiological role in cell function. In this study, we examined the content of cCMP, cAMP & cGMP and each hydrolyzing enzyme (phosphodiesterase, (PDE)) in rat thyroid during administration of LATS and TSH for 7 days (Exp. 1), and also in the thyroid of rats given methylthiouracil (MTU) for 4 months (Exp. 2). Each cyclic nucleotide was determined by RIA, and PDE activity was determined according to Kuo's method.

Exp. 1: the wet weight of thyroid in the LATS and TSH group increased 3 and 2 times respectively, from the control. Both the LATS and TSH groups showed increased plasma T4 and T3 levels. In both groups the cAMP content per wet weight of thyroid was increased slightly, but cGMP content did not change. In contrast, the cCMP content decreased markedly. Both the LATS and TSH groups showed an increase of cAMP-PDE activity in the thyroid, and no change of cGMP-PDE, while cCMP-PDE decreased markedly. In all groups levels of these 3 cyclic nucleotides and PDE activities in plasma were unaffected.

Exp. 2: in the MTU group the thyroid weight increased 4.5 times over the control, and plasma T4 and T3 levels were extremely low. The cAMP content in whole thyroid gland and also per mg wet weight was increased markedly, but cGMP content did not change. cCMP content decreased significantly. The plasma cAMP level increased slightly, but the plasma cGMP and cCMP levels did not change.

The increase of cAMP content and cAMP-PDE activity, and conversely the decrease of cCMP content and cCMP-PDE in the thyroid by LATS and TSH stimulation, suggest that cCMP may play a physiologically important role within the cells, similar to cAMP in the mechanism of hormone action.
Oestrogen synthesis by bovine foetal placenta at normal parturition
Authors: Larsson K. , Wagner W. C. , Sachs M.
Published: December 2008

In vitro conversion of C19-[3H]androstenedione and C21-[3H]pregnenolone steroids to oestrogens was studied in tissue cultures prepared from bovine cotyledons collected 10–240 min after natural parturition. A total of 17 cows was used, 15 had normal parturitions and 2 cows required assistance due to weak and prolonged labour.

At collection of tissues, blood samples were drawn from the cows and peripheral plasma oestrogen levels were determined by radioimmunoassay. Percentage conversion to unconjugated and conjugated oestrogens was estimated for each cow from 6 tissue culture replicates for each precursor. The steroids were extracted with toluene and separated by phenolic extraction and column chromatography. The repeatability of conversion rate was very high.

Incubation with androstenedione yielded consistently higher conversion rates than incubation with pregnenolone. Independent of precursor the conversion rates, within cows, ranked unconjugated Oe1 > conjugated Oe1 > unconjugated Oe2 > conjugated Oe2. The conversion rates decreased significantly with increasing intervals from parturition to collection of material. Lower conversion rates were found for cultures of tissues from the 2 cows with weak labour when compared to cultures from normally calving cows. The sire of the foetus had an influence on conversion rate in the tissue cultures. The plasma oestrogen concentrations of the cows decreased significantly with an increased interval from parturition to blood-sampling. With the exception of one cow, the tissue culture conversion rates and the plasma oestrogen levels of the cows were significantly correlated.
The relationship of plasma gonadotrophins and steroid concentrations to body growth in girls
Authors: Parra A. , Cervantes C. , Sánchez M. , Fletes L. , García-Bulnes G. , Argote R. M. , Sojo I. , Carranco A. , Arias R. , Cortés-Gallegos V.
Published: December 2008

Plasma concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), 17 alpha-hydroxyprogesterone (17α-OHP), 17β-oestradiol (Oe2) and progesterone (P) were measured in 352 healthy girls aged 6.0 to 15.9 years, as a function of age (CA), weight, height and calculated lean body mass (LBM) and total body fat (TBF). The earliest hormonal changes were a fall in mean plasma FSH concentrations together with a small but significant rise in plasma Oe2 well in advance of any sign of pubertal development. The next changes were a progressive rise in plasma FSH and 17α-OHP concentrations without further increments in plasma Oe2; these changes corresponded to a mean body weight of 29.8 kg, a mean height of 132.0 cm (initiation of the adolescent growth spurt), a mean LBM of 24.7 kg and a mean TBF of 5.1 kg. The last events were a progressive rise in plasma LH and Oe2 and less marked in P, which occurred in association with a mean body weight of 40.0 kg, a mean height of 142.0 cm (time of peak velocity of weight and height gain), a mean LBM of 31.8 kg and a mean TBF of 9.1 kg. Significant quadratic equations were disclosed between plasma FSH and LH versus CA, weight, height and LBM, and a significant linear correlation was observed between each gonadotrophin and TBF. These results show an association, not necessarily causal, between a 'critical level' of body composition and hormonal changes at the start of the adolescent growth spurt, as well as with late hormonal events at the time of peak velocity in weight and height gain. On the other hand, LBM rather than TBF seems more closely associated with the initiation and progression of puberty.
Effects of fasting on thyroid hormone levels and kinetics of reverse triiodothyronine in cattle
Authors: Blum J. W. , Kunz P.
Published: December 2008

The effects of starvation for 5 days on plasma levels, and for 3.5 days on kinetics, of 3,3′,5′-triiodothyronine (reverse T3, rT3) were studied in steers. During the 5 day starvation period alterations of plasma levels of thyroxine (T4), 3,5,3′-triiodothyronine (T3), immunoreactive insulin (IRI), glucose, free fatty acids (FFA), urea and protein were determined. During starvation rT3 did not change, while T4 and T3 (total and free), IRI and glucose decreased and FFA, urea and protein increased (P < 0.05). During re-alimentation changes of T4 and T3 (total and free), IRI, FFA and urea were partially reversed and rT3 slightly increased, but the difference was not statistically significant with respect to mean values observed during fasting. During intravenous rT3 infusions (3.85 pmol/kg/min) for 300 min in fed and fasted steers plasma rT3 levels increased rapidly, reaching steady-state levels around 2 nmol/l between 180 and 300 min, and decreased after termination of the infusions. In fed as compared to fasted animals the total clearance rate was higher (2.63 ± 0.30 and 1.72 ± 0.21 ml/kg/min, respectively; P < 0.025) and the exponential constant (k1) of the initial phase of disappearance of rT3 from plasma after the end of the infusions was greater (0.11 ± 0.02 and 0.05 ± 0.01, respectively; P < 0.025). The data show that plasma rT3 levels in steers do not increase during starvation, which is in contrast to man, rabbits and sheep. This may be due to reduced availability of T4, serving as a substrate for rT3 and to the relatively high clearance rate of rT3 even during fasting, as compared to that of rabbits and man. That energy deficiency was sufficiently severe, was suggested by the marked responses of T4, T3, IRI, glucose, FFA and urea to starvation.
Oral contraception in diabetic women. Diabetes control, serum and high density lipoprotein lipids during low-dose progestogen, combined oestrogen/progestogen and non-hormonal contraception
Authors: Rådberg Thomas , Gustafson Anders , Skryten Asbjörn , Karlsson Kirsten
Published: December 2008

Thirtyeight women with insulin-dependent diabetes were randomly allocated to contraception with either a progestogen only (Lynestrenol 0.5 mg daily) (LYN), a combined oral contraceptive (OC) (Ethinyl oestradiol 50 μg + Lynestrenol 2.5 mg) (EE + LYN) or a non-hormonal intrauterine device (IUD). Diabetes control (i.e. insulin dosage, blood and urinary glucose and body weight) and the lipid concentration in serum and in high density lipoprotein (HDL) were assessed before and during six months use of the respective contraceptives.

In the LYN group urinary glucose excretion increased 10% in spite of unchanged blood glucose, body weight and insulin requirement. All serum lipids decreased; triglycerides by 40% (P < 0.01), cholesterol by 13% (P < 0.01) and phospholipids by 12% (P = 0.06), without alteration of HDL lipids. In the group using combined OC (EE + LYN) the insulin requirement increased by 7% (P < 0.01) without any change in body weight or blood and urinary glucose. Serum as well as HDL lipids remained unchanged. In the IUD group neither diabetes control nor serum or HDL lipids were altered.

It is concluded that in insulin-dependent diabetics the progestogen (LYN) has little influence on diabetes control but has a marked, though probably not adverse, effect on lipid metabolism. The combined OC (EE + LYN) may impair glucose homeostasis slightly but has little influence on serum or HDL lipids. These findings seem to differ from those obtained in non-diabetics during administration of contraceptive steroids and these differences suggest that absence of endogenous insulin production enhances the effects of progestogen and reduces the effects of synthetic oestrogens on lipid metabolism.
Sex-specific action of antiandrogens on androgen induced changes in hepatic microsomal 3β-hydroxysteroid dehydrogenase and 5α-reductase activity in the rat
Authors: Lax E. Rodney , Schriefers Herbert
Published: December 2008

The ability of two antiandrogens, cyproterone acetate and flutamide, to block the induction of microsomal 3β-hydroxysteroid dehydrogenase and repression of microsomal 5α-reductase in rat liver following administration of 5α-dihydrotestosterone was investigated in male and female castrated and female gonadintact rats. Although both antiandrogens blocked the effects of 5α-dihydrotestosterone on the seminal vesicles and uteri of gonadectomized rats at the doses employed, cyproterone acetate showed no antiandrogenic activity against the two enzyme activities. On the contrary when cyproterone acetate was administered alone it elicited a response similar to that seen after androgen administration; when given simultaneously with 5α-dihydrotestosterone, the induction of 3β-hydroxysteroid dehydrogenase activity was greater than after either steroid alone. In contrast the non-steroidal antiandrogen, flutamide, which had no intrinsic effect on either enzyme activity, effectively blocked 5α-dihydrotestosterone mediated changes in the enzyme activities of female rats regardless of gonadal status. However the influence of 5α-dihydrotestosterone administration on these enzyme activities in male rats was not prevented.
46,XY male pseudohermaphroditism due to early foetal testicular dysgenesis
Authors: Messinis Ioannis E. , Nillius Sven Johan
Published: December 2008

A 17 year old patient with female phenotype and 46,XY karyotype presented because of primary amenorrhoea. Enlarged clitoris and pubic hair were observed and no breast development. Gonadotrophin values were greatly raised into the castrate range, while testosterone was at the upper limit of the normal range for females. No uterus, Fallopian tubes or remnants of Mullerian and Wolffian products were found at laparotomy. Bilateral inguinal masses were removed and proved to be testicular tissue. This case report shows that gonads can be present in patients with the clinical and endocrinological characteristics of the syndrome of 'true agonadism'.