bluuebunny/crossref_metadata_2025 huggingface dataset:
Immediate and time-dependent effects of glucose on insulin release: differential calcium requirements
Authors: Nesher Rafael , Praiss Michal , Cerasi Erol
Published: December 2008

Abstract. Glucose regulates insulin release in a complex manner; apart from its acute secretory action it induces time-dependent effects which modulate subsequent islet responses. The Ca2+ sensitivities of the diverse secretory events generated by glucose were investigated in the perfused rat pancreas. First- and second-phase insulin responses to 16.7 mmol/l glucose were obliterated in the presence of 5 mmol/l EgTA; threshold Ca2+ concentrations for significant responses were 0.25 mmol/l for second-phase, and 'O' (no Ca2+ added, approx 20 μmol/l) for first-phase release (both around 10% of control). The apparent Km of the Ca2+ dependencies were 0.6 mmol/l for first-phase, and 1.25 mmol/l for second-phase release. Time-dependent potentiation was demonstrated by subjecting the pancreas to two 40-min 16.7 mmol/l glucose stimuli separated by a 30-min rest period; this amplified the first-phase response to the second stimulus 2.5 ± 0.9-fold. Also the generation of potentiation was Ca2+ dependent, with characteristics similar to those of the acute secondphase insulin response (apparent Km ~1.0 mmol/l Ca2+). In contrast, the amplified first-phase response to the second glucose pulse retained its high sensitivity to Ca2+, thus resembling the unprimed first-phase. The inhibitory message of glucose was demonstrated by applying two sequential 5-min pulses of 8.3 mmol/l glucose: the insulin response to the second stimulus was reduced by 43 ± 9%. Addition of EgTA to the first glucose pulse had no effect on the inhibition of the second insulin response. Thus: 1. Despite its high sensitivity to Ca2+, also first-phase release is fully dependent on extracellular Ca2+. 2. The amplifying effect of glucose priming is Ca2+ dependent, with requirements similar to those of the acute second-phase release. 3. Amplified insulin release does not involve changes in beta cell sensitivity to extracellular Ca2+. 4. The inhibitory effect of a short glucose stimulus is not a Ca2+ dependent event. 5. These findings may relate to the Ca2+ sensitivity of distal steps in insulin release rather than reflecting changes in the Ca2+ economy of the beta cell.
The sonographical and functional sequelae of de Quervain's subacute thyroiditis: long-term follow-up
Authors: Benker G. , Olbricht Th. , Windeck R. , Wagner R. , Albers H. , Lederbogen S. , Hoff H. G. , Reinwein D.
Published: December 2008

Abstract. Fifty-three patients with subacute thyroiditis (SAT) were seen during the acute stage of the disease. HLA-Bw 35 was positive in 33 out of 39 tested patients. At first presentation, all examined patients (N = 23) had ultrasound abnormalities (generalized hypodensity, single or multiple hypodense areas). Serum T4 and/or T3 were increased in 24/52, free T4 in 11/23, and the TSH response to TRH was flat in 8/11 patients. Six of 12 in whom volumetry was performed had goitres. Thirty-seven patients were re-examined after a mean follow-up interval of 46.5 months. At this follow-up, serum T4, free T4 and T3 levels as well as the sonographically determined thyroid volume had decreased, but there was still abnormalities by ultrasound detected in 14/36 patients; 19.4% had focal sonolucent lesions, whereas the prevalence of such lesions was only 3.1% in asymptomatic controls. Three patients were subclinically hypothyroid at the follow-up, whereas all others were euthyroid. Patients with abnormal ultrasound findings were of the same age and had a similar thyroid size, but a slightly higher TSH and a significantly (P<0.02) lower free T4 than those with normal ultrasound findings. They also had a higher prevalence of thyroid autoantibodies in low titres. Serum thyroglobulin was elevated in more than half of the patients during the acute phase, but only in 1 out of 11 patients during follow-up. Thyroglobulin at the follow-up was not related to TSH, but there was a correlation with thyroid volume (r = 0.57). In conclusion, thyroid abnormalities regarding both function and ultrasound findings are sufficiently frequent after SAT to warrant close observation of the patient. Conversely, abnormal ultrasound findings and diminished thyroid function, when not explained by other factors, should suggest the possibility of past SAT.
Elevated serum oxytocin of the vasopressin-deficient Brattleboro rat is present throughout life and is not sensitive to treatment with vasopressin
Authors: Boer G. J. , van Heerikhuize J. , van der Woude T. P.
Published: December 2008

Abstract. The postnatal developmental course of the enhanced OT serum level of the vasopressin-deficient (homozygous) Brattleboro rat was investigated radioimmunochemically together with the response to treatment with Pitressin tannate. Compared with heterozygous Brattleboro (control) pups, in which serum OT appeared to have an adult value from birth onwards (about 10 pmol/l), homozygous rats had approximately 2-fold enhanced OT serum level throughout early development. Between day 55 and adulthood the levels of OT rose further to 40–50 pmol/l. A 3-day treatment with Pitressin tannate both in the period before or after the age (day 16) at which the polyuria of the homozygous Brattleboro mutant can be revealed, failed to reduce the serum OT. It was therefore concluded that the high OT serum levels in the vasopressin-deficient Brattleboro rat are not induced by osmotic imbalance, but probably originates from functional teratological aspects of the mutation.
Management of early postoperative diabetes insipidus with parenteral desmopressin
Authors: Chanson Philippe , Jedynak Charles P. , Czernichow Paul
Published: December 2008

Abstract. Management of early postneurosurgical diabetes insipidus (DI) requires parenteral vasopressin before intranasal administration of desmopressin-1 desamino-8 D arginine vasopressin (dDAVP) can be initiated. We have evaluated in 15 neurosurgical patients the effect and the tolerance of a 3-day regimen of dDAVP administered im every 12 h. Patients were randomly ascribed to one of 3 treatment groups: 1 μg (N = 6), 2 μg (N = 5) or 4 μg (N = 4) were administered twice daily. dDAVP was effective whatever the dose, and DI was corrected by the 6th h of treatment. Effects were maximal on diuresis and urinary osmolality from the 18th h onwards. The effects were sustained throughout the treatment period. Reversal to pretreatment status occurred 24 h after the last injection. Moreover, 72 h after the last injection, natremia and osmolality reached values significantly below pretherapeutic values. The tolerance was excellent: hyponatremia which occurred in 11 patients, either occasionally or throughout the treatment period, remained mild and never had clinical consequences. In conclusion, before initiation of intranasal dDAVP, a 3-day treatment by 1, 2 or 4 μg of dDAVP injected im twice daily in neurosurgical patients corrected DI. Mild overhydration owing to a positive fluid balance was a side-effect which is also encountered in other therapeutic methods necessitating meticulous control of water intake.
Sexual differentiation of oxytocin stress responsiveness: effect of neonatal androgenization, castration and a luteinizing hormone-releasing hormone antagonist
Authors: Carter D. A. , Saridaki E. , Lightman S. L.
Published: December 2008

Abstract. The plasma OT increment following stress in rats is sexually dimorphic, females exhibiting greater responses than males. We have investigated the role of neonatal androgen secretion in determining the sextypical level of response. Castration of male pups either surgically or functionally (GnRH antagonist treatment) within either 2 h or 5 days of birth did not elevate the OT responses of adult males. In contrast, androgenization of female pups (testosterone, 1.25 mg/pup) within 5 days of birth markedly reduced the OT stress responses of adults to a level insignificantly different to males. The results show that neonatal androgens can exert organizational effects on OT regulatory mechanisms. Since neonatal castration was ineffective it would appear that a prenatal defeminization or masculinization event determines OT stress responsiveness in males.
CQP 201-403, a new dopamine agonist in the treatment of hyperprolactinemia
Authors: Hanssen L. E. , Brownell J. , Halse J. , Jervell J. , Stokke K. T. , Reinlie S. , Stray-Pedersen S.
Published: December 2008

Abstract. Current drugs used for hyperprolactinemia may have severe side effects. Effects and side effects of a new propylergoline derivate (CQP 201-403 SANDOZ®) have been evaluated. Twenty-four otherwise healthy women (21–44 years) with hyperprolactinemia (35–318 μg/l) without extrasellar extension of pituitary adenomas took part in a randomized, doubleblind study. Fasting prolactin levels measured on day 7 was significantly decreased when compared with day 1 (P < 0.05) in all CQP groups, to 78% with 0.005 mg daily, to 40% with 0.015 mg daily, and to 27% with 0.025 mg CQP per day for one week. The levels in the control group did not change (96%). The area under the curve of the prolactin day curve (1–8 h after drug administration) decreased significantly (P < 0.05) at all doses when day 7 was compared with day 1, to 77% with 0.005 mg, to 51% with 0.015 mg, and to 37% with 0.025 mg CQP. No change was seen in the control group (96%). Four patients (one on 0.005 mg, one on 0.015 mg, and two on 0.025 mg) experienced orthostatic hypotension while standing blood pressure was to be measured on the first day of treatment, and they had to lie down. CQP 201-403 lowers prolactin levels in hyperprolactinemic women at all doses employed. The effect was seen after the first dose of treatment, and lasted for at least 24 h. The adverse reactions are few and tolerable, and might be less than with current bromocriptine therapy.
Studies on thyroid activity in deoxycorticosterone-salt and Goldblatt two-kidney, one-clip hypertensive rats
Authors: Vargas F. , del Rio C. Garcia , Luna J. D. , Haro J. M. , Osorio C.
Published: December 2008

Abstract. In this paper we studied the role of thyroid gland function in two experimental hypertension models with different pathophysiological mechanisms: deoxycorticosterone-salt (DOCA-salt, volume dependent) and Goldblatt 2-kidney, 1-clip (2K1C, renin dependent). DOCA-salt hypertensive rats showed lower T3 and T4 serum levels by the third week of induced hypertension. Goldblatt 2K1C hypertensive rats, however, exhibited normal values for both hormones. Treatment with thyroxine accelerated the evolution of hypertension and did not affect the PRA of DOCA-salt rats. Radiothyroidectomy inhibited DOCA-salt and Goldblatt 2K1C hypertension, and prevented the suppression of PRA in DOCA-salt rats, without altering PRA or serum aldosterone in Goldblatt 2K1C rats. These results suggest that: a) a thyroid depressing factor is not activated in Goldblatt 2K1C rats; b) thyroidectomy interferes with the suppressor effect of mineralocorticoid on renin secretion; and c) normal thyroid activity is required for the hypertensive effect of the renin-angiotensin-aldosterone system in Goldblatt 2K1C rats.
Endometrial phosphatases, β-glucuronidase and cathepsin D during menstrual cycle and pre-implantation stages of gestation in the rhesus monkey (Macaca mulatta)
Authors: Sengupta Jayasree , Talwar Deepa , Paria B. C. , Ghosh D.
Published: December 2008

Abstract. β-glucuronidase, cathepsin D, acid and alkaline phosphatases were studied in rhesus monkey endometrium during the menstrual cycle (day –6 to day + 10) and pre-implantation stages (day +3 to day +6) of gestation, with day 0 considered as the day of ovulation. Acid hydrolases exhibited low levels in proliferative phase endometria followed by their gradual rise in the secretory phase of the menstrual cycle. Despite no shifts in the levels of serum progesterone and estradiol-17β, the pre-implantation period was, however, associated with distinct changes in enzyme profiles characterized by lower absolute levels (P < 0.05) of acid phosphatase and β-glucuronidase on days 3 to 6 of gestation, whereas cathepsin D activity declined significantly (P < 0.05) on days 5 and 6. Alkaline phosphatase showed a characteristic rise during the pre-ovulatory period with a gradual lowering of its level in post-ovulatory phase endometria of a non-fertile cycle; in contrast, during early gestation, alkaline phosphatase activity showed a marked elevation (P < 0.05) on days 5 and 6 of gestation. The significance of these findings is discussed.
Subcutaneous degradation of biosynthetic human growth hormone in growth hormone deficient patients
Authors: Jørgensen J. O. L. , Flyvbjerg A. , Lauritzen T. , Ørskov H. , Christiansen J. S.
Published: December 2008

Abstract. The aim of the present study was to look further into the question of local degradation of sc injected human GH in GH deficient patients. A comparison was made of serum GH levels after constant iv and sc infusion of the same amount of GH (33 ng· kg−1·min−1) in the same 9 GH deficient patients. A 3-h lag period was interposed between the iv and the sc infusion. Iv infusion was continued for 3 h. All 9 subjects subsequently received sc infusion for 19 h and five of them continued for additionally 24 h. The mean steady state serum GH level in the nine patients was 23.1 ± 5.1 μg/l after iv and 6.8 ± μg/l after sc administration (P < 0.01). Extension of the sc infusion period in 4 of the subjects did not significantly alter the serum GH level (P > 0.15), implying that a steady state was reached. The GH in the infusion system was stable throughout a 24-h period. We therefore conclude that sc injected GH is degraded locally to a substantial extent.
Progesterone does not inhibit the increase in pituitary content of luteinizing hormone after removal of estradiol in the ewe
Authors: Tamanini C. , Crowder M. E. , Nett T. M.
Published: December 2008

Abstract. During late gestation in the ewe, the pituitary content of LH is reduced by about 95%, presumably due to the presence of high concentrations of ovarian steroids. The aim of this study was to determine whether the pituitary content of LH in the ewe can increase after long-term administration of ovarian steroids, when only estradiol (E) is removed or if both E and progesterone (P) must be withdrawn to allow synthesis of LH to occur. Ten ovariectomized ewes were treated with implants containing E and P. After 3 weeks of treatment, the E implants were removed from 5 ewes (–E+P) and both steroid implants were removed from the remaining 5 ewes (−E−P). Five ovariectomized ewes received P implants at the beginning of the experiment and these implants were left in place for the duration of the study; 5 ovariectomized ewes served as controls (C). All animals were injected with 100 μg GnRH iv 3, 6 and 9 weeks after the initiation of treatment. The area under the LH-response curve was used as an indication of the pituitary content of LH. All steroid treatments markedly reduced basal levels of LH. LH levels increased only in −E−P ewes, beginning 6 weeks after initiation of the study. After 3 weeks, −E+P and −E−P ewes released less LH (P < 0.05) in response to GnRH than did C ewes, whereas P animals did not differ from controls. LH release in response to GnRH in −E+P and −E−P groups had increased by 6 and 9 weeks and was not different from that of C ewes. After 9 weeks, LH release in P ewes was reduced (P < 0.05) compared with C ewes. These data suggest that, after the pituitary content of LH has been suppressed by ovarian steroids, the presence of P alone does not inhibit replenishment of the pituitary content of LH.
Effects of busulfan on ovarian folliculogenesis, steroidogenesis and anti-müllerian activity of rat neonates
Authors: Pelloux M. C. , Picon R. , Gangnerau M. N. , Darmoul D.
Published: December 2008

Abstract. Pregnant rats were injected with busulfan on day 12 or 18 of gestation and the ovaries of 5- and 10-day-old neonates were compared with control ones in terms of 1) folliculogenesis, 2) production of estradiol-17β and estrone in vitro, 3) aromatase and 3β-hydroxysteroid dehydrogenase/isomerase (3β-HSD) activities, and 4) anti-müllerian hormone. Injection of busulfan on day 12 led to a reduction in the number of germ cells and follicles, delayed the maturation of antral follicles and lowered estrogen production and aromatase and 3β-HSD activities. Anti-müllerian activity, present in ovaries from 10-day-old controls, was also depressed in busulfan-treated rats. No obvious effects were observed when busulfan was injected on day 18. Estrogen biosynthesis could be stimulated by gonadotropins at day 10 post-partum, indicating the presence of functional receptors to LH and/or FSH. These relationships are interpreted as indicating that ovarian cells retain their capacity to respond to hormonal challenge despite the morphological impairment induced by busulfan. Other factors which possibly interfere with ovarian activity in busulfan-treated rats are discussed.
Opposing effects of glucose and tolbutamide on the sodium content of rat pancreatic islets
Authors: Ali Liaquat , Wesslén Nils , Hellman Bo
Published: December 2008

Abstract. Integrating flame photometry was employed for measuring sodium in rat pancreatic islets incubated in media buffered with HEPES or bicarbonate. The sodium content decreased by nearly 40% when the islets were exposed to 5 mmol/l glucose, no further reduction being seen with additional rise of the concentration to 20 mmol/l. Whereas the depressing effect of glucose was mimicked by 100 μmol/l quinine, increased sodium contents were noted after inhibition of the Na/K pump (removal of extracellular K+ or addition of 1 mmol/l ouabain) or exposure of the islets to 1 mmol/l tolbutamide. Although promoting sodium accumulation in the islet cells, tolbutamide counteracted the increase in sodium obtained on withdrawal of K+ from the incubation medium. It is suggested that tolbutamide in addition to its major effect in promoting the entry of Ca2+ also facilitates insulin release by suppressing the outward transport of this ion.
On the activities of parathyroid hormone-like factor and transforming growth factors in extract of pancreatic cancer associated with humoral hypercalcemia of malignancy
Authors: Akatsu Takuhiko , Nagata Naokazu , Kugai Nobuo , Yasutomo Yoshirou , Kinoshita Tokuyasu , Kosano Hiroshi , Takatani Osamu , Takishima Kunio , Mamiya Gunzi
Published: December 2008

Abstract. Extract of exocrine pancreatic cancer associated with humoral hypercalcemia of malignancy was examined for biological activities of PTH-like factor and transforming growth factor (TGFA and TGFB), both of which are possible causes of hypercalcemia. The crude extract had both PTH-like and TGF activities. On Bio Gel P-60 column chromatography, PTH-like and TGFA activities were eluted at around 10 kD, whereas TGFB activity was eluted at around void fractions, 10 kD and 6 kD. Liver extract, used as a control material, exhibited only TGFB activity at around 6 kD. CM-cellulose column chromatography of 10 kD fractions resulted in a subtle distinction between PTH-like activity and TGF activities. Further fractionation of the peak with PTH-like activity on reverse-phase high performance liquid chromatography separated PTH-like activity distinctly from TGFB activity. TGFA activity was lost through the procedure. It was concluded that the exocrine pancreatic cancer associated with hypercalcemia produced not only PTH-like activity but also TGFA and TGFB activities. Several chromatographic analyses suggested that PTH-like activity and at least TGFB activity stem from distinct molecules and that the PTH-like factor has no significant TGFB activity intrinsically.
Atrial natriuretic peptide secretion in response to volume expansion and contraction in normal man
Authors: Sakamoto H. , Marumo F.
Published: December 2008

Abstract. The plasma concentrations of ANP in response to isotonic saline-induced volume expansion and furosemide-induced volume contraction in 12 healthy men were measured by radioimmunoassay. The total ANP content was calculated by multiplying the circulating plasma volume (CPV) with the plasma ANP concentration, assuming that most of the ANP remained in the blood vessels. In addition, extracellular fluid volume (ECFV) was measured. After overnight dehydration, plasma ANP concentration significantly increased after isotonic saline was infused, but the urinary ANP concentration did not change essentially. After furosemide-induced volume concentration, plasma ANP concentrations significantly decreased, but the urinary ANP concentrations did not change essentially. As the CVP and ECFV changed, the total plasma ANP also changed. The correlation between these effects was highly significant (r = 0.84 and 0.67, N = 11, respectively). The chromatogram obtained from the plasma in the dehydrated state showed that the area of the high molecular weight ANP peak was relatively large compared with the total area of all ANP peaks. This area of the high molecular weight ANP peaks decreased after saline infusion. In the urine, only the α-ANP peak was noted and no high molecular weight ANP peak appeared in the chromatogram. These results indicate that amount and type of ANP secretion may change depending on circulating plasma volume.
Influence of season and social environment on basal and thyrotropin releasing hormone-induced prolactin secretion in the adult domestic boar
Authors: Trudeau V. L. , van de Wiel D. F. M. , Erkens J. , Sanford L. M.
Published: December 2008

Abstract. Basal and TRH-induced PRL secretions were investigated for adult Landrace boars housed in two social environments. Socially nonrestricted boars (N = 4) were individually penned adjacent to ovariectomized gilts that were hormonally induced into estrus every 3 weeks, while socially restricted boars (N =4) were individually kept in pens with solid walls. In February, May and August all boars were fitted with jugular catheters for serial blood sampling which took place 2 h prior to and 4 h following in iv injection of TRH (1 μg/kg). Mean pre-injection serum PRL concentration was not influenced by either month or social environment. The PRL response to TRH injection, however, was influenced by both factors. The magnitude of the PRL response (peak Δ value) increased (month, P < 0.01) progressively in both groups of boars from February through August and was greater (P < 0.05) in the nonrestricted versus the restricted boars in August. The total amount of PRL secreted was also maximal and greater in the socially nonrestricted boars in August (month × social group, P < 0.05). These results indicate that TRH-induced and not basal PRL secretion is influenced by both season and social interaction of boars.
Characterization of a factor from human ovarian follicular fluid which stimulates Leydig cell testosterone production
Authors: Khan S. A. , Hallin P. , Bartlett J. , De Geyter Ch. , Nieschlag E.
Published: December 2008

Abstract. A factor from human ovarian follicular fluid (hFF) has been characterized which stimulates testosterone production of human, rat, mouse and hamster Leydig cells. hFF was obtained from women participating in an in vitro fertilization programme. Basal and hCG stimulated testosterone production of rat interstitial cells, and Percoll purified Leydig cells were significantly stimulated by hFF. The steroidogenic response of the cells was 3–5 fold higher than that obtained after stimulation with maximal doses of hCG. A serum pool from the same patients was found to be about 30 times less potent than hFF in stimulating steroidogenesis. The stimulatory activity was retained after precipitation with ammonium sulphate and dialysis. Precipitation with ethanol, ether and acetone resulted in a partial loss of activity, whereas extraction with charcoal or heating at 100°C for 10 min resulted in significant loss of activity. When hFF was fractionated by gel chromatography, the stimulatory activity was eluted in a molecular weight region between 30 and 50 kD. The stimulatory factor was further purified by chromatofocusing and was eluted as a homogeneous peak with an isoelectric point between 8.8 and 9.5. The SDS-PAGE analysis of these fractions, however, revealed that the active substance was not homogeneous. The purified factor was immunologically distinct from hCG and hLH. These studies demonstrate for the first time the presence of a factor in the hFF which may potentiate the action of LH in the ovary.
Adenylate cyclase stimulation and luteinizing hormone-receptor interaction in plasma membranes from rat testicular interstitial cells in relation to the chemical structure of the hormone. Role of Mg2+
Authors: de la Llosa-Hermier M. P. , Saltarelli D. , Jammes H. , de la Llosa P. , Hermier C.
Published: December 2008

Abstract. To understand more closely the structural requirements of the LH molecule necessary to stimulate adenylate cyclase, we studied the modulation of this enzyme in partially purified plasma membranes prepared from isolated interstitial cells of rat testis submitted to oLH and to some oLH derivatives and natural analogues. The role of Mg2+ was also investigated in relation to the structural modifications of oLH. Some new facts appeared in this study: 1. Methyl oLH, which exhibited the same ability as native oLH to stimulate cAMP accumulation and steroidogenesis in isolated cells, cannot induce the same level of maximal stimulation of adenylate cyclase as native oLH in plasma membranes. This phenomenon is related to the Mg2+ concentration, and the differences between maximal activation induced by methyl oLH and oLH were more apparent at a free Mg2+ concentration of 3.3 mmol/l than at lower concentrations. The maximal activity (in terms of native oLH) of other alkyl derivatives, such as ethyl or isopropyl oLH, on the contrary, was similar in isolated plasma membranes and in intact cells suggesting that the differential behaviour of the membranes specifically concerns the methyl derivative. 2. Guanidyl oLH and guanidyl porcine LH, which were able to induce cAMP accumulation in intact cells, did not exhibit any stimulating activity in plasma membranes. 3. Among the natural analogues, hCG and pLH are distinguished by a lower maximal activity (by comparison with oLH) particularly at high Mg2+ concentration. This work shows that changes in the LH structure have an impact not only on the parameters of the adenylate cyclase complex but also on the transduction of the hormone signal and its modulation by Mg2+.
Circulating levels of 1,25 dihydroxyvitamin D, alkaline phosphatase, hydroxyproline, and osteocalcin associated with antler growth in white-tailed deer
Authors: Van Der Eems Karen L. , Brown Robert D. , Gundberg Caren M.
Published: December 2008

Abstract. Alkaline phosphatase, hydroxyproline, osteocalcin, and 1,25(OH)2D were measured in biweekly serum samples obtained from 6 adult (> 4 years), 4 juvenile (1–4 years) and 4 fawn (< 1 year) male white-tailed deer from Oct. 1983 to Oct. 1984. Antler length, from the pedicle to the tip, was measured at the time of serum sampling. Serum alkaline phosphatase activity and levels of hydroxyproline and osteocalcin were higher (P < 0.05) in fawns compared with juveniles and adults reflecting increased bone metabolism in the younger deer. In adult deer serum alkaline phosphatase activity and hydroxyproline levels were elevated (P < 0.05) during the period of antler growth, whereas serum osteocalcin and 1,25(OH)2D increased (P < 0.05) during antler mineralization. Similar but less pronounced trends occurred in juvenile deer, possibly a reflection of skeletal growth in the younger animals. The data lend support for utilization of the deer antler cycle as a model for studies of bone disorders. Further work is needed to help clarify the role of hydroxyproline, osteocalcin, and 1,25(OH)2D in the antler cycle.
Islet secretion of immunoreactive thyrotropin-releasing hormone and the 'paracrine-like' effects of its exogenous administration
Authors: Vara E. , Tamarit-Rodríguez J.
Published: December 2008

Abstract. In order to know more about the secretory pattern of islet TRH in response to glucose and its possible physiological relevance, the release of this hormone as well as that of insulin, glucagon, and somatostatin was radioimmunologically measured. Whereas the secretion of immunoreactive insulin and somatostatin by incubated rat islets is known to be dose-dependently stimulated by glucose, that of glucagon and TRH was inhibited by glucose. Similarly, palmitate dose-dependently inhibited islet glucagon and TRH release. Exogenous TRH exerted strong and dose-dependent effects on islet secretion of the other hormones at the same concentration range at which its hypophysiotropic effects are produced (10−10 to 10−8 mol/l). It inhibited the insulin response to glucose and blocked that of glucagon, whereas it enhanced glucose-induced stimulation of somatostatin. These results are suggestive of a possible paracrine inhibitory role of islet TRH, either directly exerted on the secretion of insulin and glucagon or partially mediated through the stimulation of somatostatin release.
Decreased TSH response to TRH induced by amiodarone
Authors: Lambert M. , Burger A. G. , De Nayer P. , Beckers C.
Published: December 2008

Abstract. In order to test the reactivity of TSH to TRH during amiodarone treatment we investigated 7 hypothyroid subjects treated with 50 μg T3/day. A TRH test (200 μg iv) was performed before and after 6 weeks of treatment with 400 mg amiodarone/day. Amiodarone treatment induced a significant increase in serum total and free T3 (from 2.17 ± 0.13 to 3.55 ± 0.58 nmol/l and from 5.6 ± 0.61 to 9.46 ± 1.41 pmol/l). Basal TSH levels were significantly decreased and the maximal stimulation of TSH 20 min after TRH injection was only 20.0 ± 3.3 mU/l during amiodarone treatment compared with 61.4 ± 10.4 mU/l before treatment. These results indicate that in hypothyroid patients treated with amiodarone, the TSH response to TRH is blunted and that this is likely to be related to the higher total and free T3 levels or to a direct effect of amiodarone at the pituitary level.
Quantitative assessment of the ontogeny of met-enkephalin, norepinephrine and epinephrine in the human fetal adrenal medulla
Authors: Wilburn Linda A. , Jaffe Robert B.
Published: December 2008

Abstract. The catecholamine producing cells of the adrenal medulla of fetal as well as adult mammals contain enkephalins. We have quantified met-enkephalin and the catecholamines, norepinephrine and epinephrine in human fetal adrenal glands during the late first trimester and throughout the second trimester of intrauterine life. Met-enkephalin (ME) was detectable in human fetal adrenals of 11 to 25 weeks' gestation by RIA. ME concentrations were low through 14 weeks (mean 279 ± 199 pg/gland), higher but extremely variable from 15 to 20 weeks (mean 1100 ± 1000 pg/gland), and then lower with somewhat less variation through 25 weeks (mean 865 ± 625 pg/gland). In contrast, catecholamine concentrations were below 1100 ng/gland through 16 weeks, then increased markedly by 21 weeks. Approximately equal concentrations of norepinephrine and epinephrine were measured throughout the gestational age period studied. Our data demonstrate that enkephalin is present in the human fetal adrenal at least by 11 weeks' gestation and suggest that the fetal adrenal may be capable of secreting enkephalins as well as catecholamines. The functional significance of adrenal enkephalin secretion remains to be elucidated.
IgA class antibodies against Yersinia enterocolitica O:3 in patients with thyroid disease
Authors: Leino Rauli , Lahesmaa-Rantala Riitta , Granfors Kaisa , Toivanen Auli
Published: December 2008

Abstract. IgM, IgG and IgA class serum antibodies against Yersinia enterocolitica O:3 and O:9 and Yersinia pseudotuberculosis la and 3 in 41 patients with thyroid disease and 50 healthy control persons were measured by enzyme-linked immunosorbent assay (ELISA). Concentrations of antibody levels against Yersinia enterocolitica O:9 and Yercinia pseudotuberculosis la and 3 did not differ significantly between the patients and controls. The median value of IgA class antibody Yersinia enterocolitica O:3 was 7.5 relative units (EIU, percentage of the reference serum) in the patients with thyroid disease and 0.7 EIU in the controls (P<0.01; Mann-Whitney's U-test), whereas IgM and IgG class antibodies did not show this difference. IgA class serum antibodies were especially high in patients with autoimmune thyroid diseases. These findings and two case reports support the concept that there may be a causal relationship between infections with Yersinia enterocolitica O:3 and autoimmune thyroid diseases.
Effects of galanin on the release of insulin, glucagon and somatostatin from the isolated, perfused dog pancreas
Authors: Hermansen K.
Published: December 2008

Abstract. Galanin is a 29 amino acid peptide which has been found in intrapancreatic nerves. The effects of galanin, adrenergic and cholinergic blockade as well as somatostatin on the hormone release from the isolated perfused dog pancreas were studied. It was found that galanin dose-dependently inhibited insulin (P < 0.001) and somatostatin (P < 0.001) but not glucagon secretion at normal glucose levels. The lowest galanin concentration that caused a significant suppression of insulin and somatostatin secretion was 10−11and 10−10 mol/l, respectively. Similar effects were evident during stimulation with 2.5 mmol/l arginine. Galanin (10−9 mol/l) caused a more pronounced inhibition of insulin and somatostatin secretion at high (10 mmol/l) and normal (5 mmol/l) than at low glucose (1.3 mmol/l). In contrast, suppression of the glucagon secretion was only seen at low glucose (1.3 mmol/l). Perfusion of 10−6 mol/l of atropine, phentolamine and propranolol had no effect on the galanin-mediated (10−10 mol/l) inhibition of insulin and somatostatin secretion. Galanin (10−12–10−10 mol/l) and somatostatin (10−12 – 10−10 mol/l) were equipotent in inhibiting insulin secretion whereas only somatostatin exerted a suppression of the glucagon secretion at normal glucose. Thus, galanin exerts a differential effect on islet hormone secretion and may participate in the hormonal control of insulin, glucagon and somatostatin secretion.
Can serum thyroglobulin predict the effect of thyroid hormone therapy on goitre growth?
Authors: Bürgi U. , Scazziga B. R. , Rosselet P. O. , Bürgi H. , Studer H.
Published: December 2008

Abstract. Serum thyroglobulin and goitre size were followed in 22 patients with simple goitre or single thyroid nodules during 9 months of thyroxine therapy, to see whether alterations in serum thyroglobulin correlated with changes in goitre size. In the case of such a correlation serum thyroglobulin could be used to predict which goitres respond to thyroxine therapy and which require surgery. Pretreatment serum thyroglobulin was elevated in 11 patients. It normalized in one of 7 patients whose goitre did not shrink and in none of the 4 patients whose goitre shrank during thyroxine treatment. Thus no simple correlation exists between alterations in serum thyroglobulin and goitre size during short-term thyroxine therapy. Since other studies suggest that increased serum thyroglobulin indicates ongoing goitre growth, thyroxine treatment might have been unsuccessful in all patients with persistently elevated serum thyroglobulin with a longer follow-up. The presence of predominantly thyroxine responsive tissue together with some autonomously growing, thyroglobulin-releasing areas in the same goitre could explain the failure of serum thyroglobulin to normalize in patients whose goitre shrank during therapy. The study shows that after eradication of iodine deficiency, thyroxine treatment is rarely successful in the Swiss goitre population and that surgical treatment is usually required.
Treatment of hyperthyroidism with a small single daily dose of methimazole
Authors: Mashio Yasuo , Beniko Mutsuo , Ikota Akemi , Mizumoto Hiroaki , Kunita Haruhiko
Published: December 2008

Abstract. A prospective randomized trial with the conventional divided doses (10 mg 3 times daily, N = 29) and a small single daily dose (15 mg once daily, N = 25) of methimazole for the treatment of Graves' hyperthyroidism was performed. Within 8 weeks, almost 80% of the patients in both groups became euthyroid. The mean time required to achieve the euthyroid state was 6.0 ± 2.8 and 6.0 ± 3.8 weeks, respectively. TSH binding inhibitor immunoglobulin was found in about 90% of the patients in both groups before methimazole treatment. However, a gradual fall of its levels was observed in nearly all patients after treatment. There was no difference in the mean levels of TSH binding inhibitor immunoglobulin between the two groups during therapy. We conclude that the single daily dose regimen of 15 mg of methimazole will control Graves' hyperthyroidism in most patients, and TSH binding inhibitor immunoglobulin levels decrease in this regimen in the same way as with the conventional divided dose regimen (10 mg 3 times daily).
The inhibitory effect of iodide on growth of rat thyroid (FRTL-5) cells
Authors: Saji Motoyasu , Isozaki Osamu , Tsushima Toshio , Arai Mariko , Miyakawa Megumi , Ohba Yoshito , Tsuchiya Yumi , Sano Tomohide , Shizume Kazuo
Published: December 2008

Abstract. The effect of iodide on growth of rat thyroid cells (FRTL-5) was studied. TSH-stimulated cell growth was inhibited by iodide in a concentration-dependent manner, and an effect of iodide was detected at 10−6 mol/l. KClO4 or 1-methylimidazole-2-thiol blocked the effect of iodide, suggesting that iodide uptake and its organification are required to produce the inhibitory effect of iodide on cell growth. Iodide not only decreased TSH-stimulated cAMP production in FRTL-5 cells but also cell growth induced by cAMP. These observations suggest that iodide inhibits TSH-stimulated growth of the cells by attenuating cAMP production and also by acting on the step(s) distal to cAMP generation. The inhibitory effect of iodide was also seen in growth stimulated by insulin, insulin-like growth factor-I or 12-O-tetradecanoyl phorbol 13-acetate, suggesting multiple sites of action of iodide in the process of growth of FRTL-5 cells.
Clinical response of thyrotropin-secreting macroadenoma to bromocriptine and radiotherapy
Authors: McLellan A. R. , Connell J. M. C. , Alexander W. D. , Davies D. L.
Published: December 2008

Abstract. A patient presenting with hyperthyroidism was treated initially with antithyroid drugs and subsequently radioiodine. Thereafter he was noted to have inappropriately elevated thyrotropin. A bitemporal visual field defect was noted and CT scan confirmed the presence of a pituitary tumour. TSH was elevated and unresponsive to TRH stimulation. α subunit was not elevated. Long-term bromocriptine therapy (doses up to 50 mg/day) resulted in partial, but incomplete suppression of thyrotropin secretion. Following radiotherapy there was resolution of the visual field defect; the TSH, however, remains elevated at > 20 mU/l. radiotherapy and bromocriptine may provide a clinically useful alternative to pituitary surgery in patients with TSH-secreting macroadenoma with suprasellar extension.
Influence of starvation on hormonal control of hypophyseal secretion in rats
Authors: Hugues Jean-Noel , Epelbaum Jacques , Voirol Marie-Jeanne , Modigliani Elisabeth , Sebaoun Jacques , Enjalbert Alain
Published: December 2008

Abstract. The reduction of hypophyseal hormone secretion during starvation is not completely understood. A previous study showed that the concomitant reduction of plasma TSH and T3 may be related to an increased sensitivity of the thyrotrope cell to T3. This suggests that regulation of hypophyseal secretion by peripheral hormones may be altered in starved rats. As GH and PRL secretion are under the control of thyroid and steroid hormones, the aim of the present study was to investigate the modification of feed-back control by T3 or E2 on hypophyseal secretion during starvation. For this purpose, pituitary GH, PRL and TSH contents and their plasma responses to TRH injection were measured in euthyroid, thyroidectomized (Tx), T3-supplemented Tx and E2-treated male Wistar rats before and after a 3-day starvation. TRH (0.25 μg/100 g) was injected iv through a chronically-implanted catheter. Our results show that GH content and GH plasma response to TRH are dramatically increased in T3-treated Tx starved rats, suggesting that starvation also increases the effectiveness of T3 influence on somatotrope cell secretion. By contrast, effects of T3 on PRL secretion remain unchanged during starvation. Furthermore, starvation in E2-treated rats is associated with a marked rise in the PRL and GH responsiveness to TRH without any significant change of hormonal pituitary content. This suggests that, in starved rats, E2 increases the effects of TRH on lactotrope and somatotrope secretion. No significant effect on TSH secretion could be demonstrated. Thus, starvation seems to act differentially on the feed-back mechanisms controlling the hormonal secretion of the three adenohypophyseal target cells to TRH.
Quantitation of uncombined gonadotropin subunits within and released by the rat anterior pituitary
Authors: Grotjan H. Edward
Published: December 2008

Abstract. The release of uncombined gonadotropin subunits by rat anterior pituitaries during an in vitro incubation as well as intracellular concentrations were assessed. Uncombined subunits and native gonadotropins were quantitated by radioimmunoassays after samples were subjected to gel filtration on Sephadex G-100 Superfine. Small, but detectable, amounts of uncombined rat LH β subunit were released under basal conditions. GnRH increased the absolute amount of rLHβ released but did not alter the rLHβ/rLH molar ratio (≈ 0.02). Tissue extracts prepared in aqueous buffer (100 000 × g supernatants) and 0.5% Triton X-100 extracts of the 100 000 × g pellets from the initial homogenization ('pellet extracts') contained larger quantities of uncombined rLHβ as well as elevated rLHβ/rLH molar ratios (≈ 0.10 and ≈ 0.20, respectively). Significant amounts of uncombined rLHα were released and were present in both tissue and pellet extracts. However, when FSH β subunit was quantitated in tissue extracts after gel filtration, all of the immunoreactive materials eluted in the position of native rFSH (FSHβ/rFSH molar ratio < 0.0025). Pellet extracts contained significant amounts of rLHβ, rLH and rLHα but lesser amounts of rFSH suggesting that intracellular gonadotropins are not completely extracted when homogenization is performed in aqueous buffers. Thus, rat anterior pituitaries contain and release significant amounts of the uncombined α subunit, relatively small amounts of uncombined rLHβ and extremely small amounts of uncombined FSHβ, if any.
Characterization of the insulin resistance of glucose utilization in adipocytes from patients with hyper- and hypothyroidism
Authors: Pedersen Oluf , Richelsen Bjørn , Bak Jens , Arnfred Jon , Weeke Jørgen , Schmitz Ole
Published: December 2008

Abstract. Insulin action on glucose utilization was characterized in adipocytes from 10 thyrotoxic patients, 6 hypothyroid patients and 10 age- and sex-matched control subjects. In thyrotoxic patients insulin binding at low insulin concentrations was reduced (P < 0.05) and accompanied by impaired insulin sensitivity of glucose transport (P < 0.02), glucose oxidation (P < 0.05) and lipogenesis (P < 0.05). Glucose transport and glucose oxidation rates also exhibited depressed maximal insulin responsiveness (P < 0.05). In hypothyroid patients insulin binding was reduced, too, (P < 0.05) and associated with impaired sensitivity to insulin of glucose transport (P < 0.05). Both glucose transport and lipogenesis rates showed decreased maximal insulin responsiveness (P < 0.05). In conclusion: In man, both hyper- and hypothyroidism are characterized by insulin resistance of adipocyte glucose utilization localized to insulin binding as well as to insulin-stimulated glucose transport and metabolism.
Linkage of HLA-DRβ specific restriction fragment length polymorphisms with Graves' disease
Authors: Boehm B. O. , Schifferdecker E. , Kuehnl P. , Schöffling K.
Published: December 2008

Abstract. HLA-DR3 positive patients with Graves' disease (6 homozygotes, 7 heterozygotes, i.e. yielding 19 haplotypes) were studied by restriction fragment length polymorphism analysis using TaqI as restriction enzyme in order to look for polymorphisms in the HLA-DR3 allele of the human major histocompatibility complex. Polymorphic TaqI fragments of 11.6, 9.8 and 5.8 kb, each corresponding to HLA-DRβ sequences, were shown to differ in their prevalence in patients with Graves' disease and controls. The prevalence of DR3 polymorphisms in a total of 35 HLA-DR3-containing haplotypes was markedly different within patients with Graves' disease and Caucasian controls. Whereas a 11.6 kb fragment was rare in Graves' disease (2/19 haplotypes vs 8/16 in controls), the inverse ratio was found for a 9.8 kb fragment, with a prevalence of 17/19 and 8/16 haplotypes, respectively. A polymorphic fragment of 5.8 kb was exclusively seen in two DR3-containing haplotypes of patients with Graves' disease. Our data provide evidence that a DNA polymorphism of the HLA-DRβ genes, which is also reflected at the product level, is linked to Graves' disease.
Hormonal responses to synthetic atrial natriuretic peptide in patients on regular hemodialysis
Authors: Nakajima Sadao , Suzuki Hiromichi , Kageyama Yo , Takita Takashi , Saruta Takao
Published: December 2008

Abstract. The effects of atrial natriuretic peptide (ANP) on mean arterial blood pressure, heart rate, plasma renin activity, aldosterone, cortisol, norepinephrine, epinephrine and arginine vasopressin were studied in 6 anuric subjects receiving regular hemodialysis. An iv bolus injection of 8 nmol of ANP followed by infusion at 32 pmol·kg−1·min−1 for 1 h in the pre- and posthemodialysis period was performed. Basal plasma ANP was higher before than after hemodialysis. ANP administration produced a reduction in mean arterial blood pressure accompanied by an elevation of norepinephrine and of plasma renin activity (from 2.49 ± 0.52 to 3.39 ± 0.85 nmol·l−1·h−1 predialysis and from 2.78 ± 0.71 to 3.15 ± 0.86 nmol·l−1·h−1 postdialysis, respectively, mean ± sem; P < 0.05). Plasma aldosterone and cortisol were significantly decreased. Plasma epinephrine and AVP remained unchanged. These hemodynamic and hormonal changes were similar in the pre- and the postdialysis period. These results suggest that 1) ANP causes a fall in mean arterial blood pressure, which in turn induces reflex tachycardia and activation of the sympathetic nervous system without diuresis; 2) the activated sympathetic nervous system as reflected in elevation of plasma norepinephrine may increase plasma renin activity; 3) reduced plasma aldosterone is not influenced by enhancement of the reninangiotensin system; therefore, 4) reduction of plasma aldosterone as well as cortisol is probably due to direct action of ANP, and finally 5) AVP had no direct relation with ANP administration.