bluuebunny/crossref_metadata_2025_split huggingface dataset:
Growth hormone-releasing factor expression is discordantly regulated in the hypothalamus and testis of streptozotocin-diabetic rats
Authors: Olchovsky D , Bruno J F , Berelowitz M 
Published: December 2004

Abstract
Growth hormone-releasing factor (GRF) mRNA expression in male rats occurs predominantly in the hypothalamus (mainly in the arcuate nucleus), and among extraneural sites primarily in the testis. Hypothalamic GRF is the physiological tropic stimulus to growth hormone secretion. However, the role of GRF in the testis is unknown. We have shown previously that hypothalamic GRF mRNA expression is significantly reduced in streptozotocin (STZ)-diabetic rats. This reduction is confined to the arcuate nucleus and probably accounts for the suppression of growth hormone pulsatility.
The present studies were performed to evaluate GRF expression in the testis of streptozotocin (STZ)-diabetic rats. Diabetes was induced by injection of STZ (100 mg/kg i.p.). Seventeen to twenty days later diabetic rats were hyperglycemic compared with vehicle-injected controls and demonstrated growth failure. Insulin treatment reduced the glycemia and increased body weight towards normal. Total RNA was extracted from the hypothalamus and testis, and GRF mRNA levels estimated by solution hybridization/nuclease protection assay. Levels of hypothalamic somatostatin mRNA were measured to serve as control values. GRF mRNA was significantly (P<0·001) decreased in the hypothalamus of STZ-diabetic rats (0·2 ± 0·07 mean relative densitometric units, n=8) compared with controls (1·0 ± 0·19, n=8) with no change in somatostatin mRNA expression. In contrast, testicular GRF mRNA was increased 70% (P<0·05) in STZ-diabetic rats. Insulin treatment resulted in normalization of hypothalamic GRF mRNA levels (1·1 ± 0·17, n=5) with no effect on testicular GRF mRNA expression.
In conclusion GRF gene expression is discordantly regulated in tissues of male STZ-diabetic rats. While reduced GRF expression may account for the low growth hormone state in this model, increased testicular GRF mRNA (with the previously reported reduction of insulin-like growth factor-I mRNA) resembles the response seen in growth hormone-sensitive tissue (especially the hypothalamus) to this growth hormone-deficient state.
Journal of Endocrinology (1996) 148, 189–192
The effects of GH-releasing peptide-6 (GHRP-6) and GHRP-2 on intracellular adenosine 3′,5′-monophosphate (cAMP) levels and GH secretion in ovine and rat somatotrophs
Authors: Wu D , Chen C , Zhang J , Bowers C Y , Clarke I J 
Published: December 2004

Abstract
The mechanism of action of GH-releasing peptide-6 (GHRP-6) and GHRP-2 on GH release was investigated in ovine and rat pituitary cells in vitro. In partially purified sheep somatotrophs, GHRP-2 and GH-releasing factor (GRF) increased intracellular cyclic AMP (cAMP) concentrations and caused GH release in a dose-dependent manner; GHRP-6 did not increase cAMP levels. An additive effect of maximal doses of GRF and GHRP-2 was observed in both cAMP and GH levels whereas combined GHRP-6 and GHRP-2 at maximal doses produced an additive effect on GH release only. Pretreatment of the cells with MDL 12,330A, an adenylyl cyclase inhibitor, prevented cAMP accumulation and the subsequent release of GH that was caused by either GHRP-2 or GRF. The cAMP antagonist, Rp-cAMP also blocked GH release in response to GHRP-2 and GRF. The cAMP antagonist did not prevent the effect of GHRP-6 on GH secretion whereas MDL 12,330A partially reduced the effect. An antagonist for the GRF receptor, [Ac-Tyr1,d-Arg2]-GRF 1–29, significantly diminished the effect of GHRP-2 and GRF on cAMP accumulation and GH release, but did not affect GH release induced by GHRP-6. Somatostatin prevented cAMP accumulation and GH release responses to GHRP-2, GRF and GHRP-6. Ca2+ channel blockade did not affect the cAMP increase in response to GHRP-2 or GRF but totally prevented GH release in response to GHRP-2, GRF and GHRP-6. These results indicated that GHRP-2 acts on ovine pituitary somatotrophs to increase cAMP concentration in a manner similar to that of GRF; this occurs even during the blockade of Ca2+ influx. GHRP-6 caused GH release without an increase in intracellular cAMP levels. GH release in response to all three secretagogues was reduced by somatostatin and was dependent upon the influx of extracellular Ca2+. The additive effect of GHRP-2 and GRF or GHRP-6 suggested that the three peptides may act on different receptors. In rat pituitary cell cultures, GHRP-6 had no effect on cAMP levels, but potentiated the effect of GRF on cAMP accumulation. The synergistic effect of GRF and GHRP-6 on cAMP accumulation did not occur in sheep somatotrophs. Whereas GHRP-2 caused cAMP accumulation in sheep somatotrophs, it did not do so in rat pituitary cells. These data indicate species differences in the response of pituitary somatotrophs to the GHRPs and this is probably due to different subtypes of GHRP receptor in rat or sheep.
Journal of Endocrinology (1996) 148, 197–205
Possible mechanism for the first response to short captivity stress in the water frog, Rana esculenta
Authors: Gobbetti A , Zerani M 
Published: December 2004

Abstract
To clarify the endocrine mechanism involved in the short captivity stress in the water frog, Rana esculenta, the activity of 9-ketoreductase, the enzyme which converts prostaglandin E2 (PGE2) into prostaglandin F2α (PGF2α), and aromatase, which converts testosterone into oestradiol-17β, were studied. Adult male and female frogs were sacrificed 0, 1·5, 3, 6, 12, 24, 48, 72, 168 and 336 h after capture in the field. PGE2, PGF2α, progesterone, testosterone, oestradiol-17β and corticosterone plasma levels were detected by RIA at each time point. 9-Ketoreductase (conversion of [3H]PGE2 into [3H]PGF2α) and aromatase (conversion of [3H]testosterone into [3H]oestradiol-17β) activities in the brain, testis, ovary and interrenal were also determined at each time point. After capture, levels of plasma PGF2α increased (male: 228%; female: 288%) and PGE2 decreased (male: 68%; female: 81%) at 1·5 h, oestradiol-17β increased (male: 399%; female: 425%) and testosterone decreased (male: 87%; female: 83%) at 6 h, and corticosterone increased (male: 421%; female: 426%) at 72 h. 9-Ketoreductase activity in the brain was enhanced at 1·5 h after capture (male: 249%; female: 262%); aromatase activity increased at 6 h in the testis (261%), ovary (273%) and interrenal (male: 227%; female: 267%). These results indicate that short captivity stress could induce an increase in plasma PGF2α through activation of brain 9-ketoreductase. In turn, PGF2α might enhance the levels of circulating oestradiol-17β through activation of gonadal and interrenal aromatase.
Journal of Endocrinology (1996) 148, 233–239
Studies on the role of TRH and corticosterone in the regulation of prolactin and thyrotrophin secretion during lactation
Authors: van Haasteren G A C , van Toor H , Klootwijk W , Handler B , Linkels E , van der Schoot P , van Ophemert J , de Jong F H , Visser T J , de Greef W J 
Published: December 2004

Abstract
This study describes the effects of litter size and acute suckling on the synthesis and release of hypothalamic TRH, as indirectly estimated by determination of hypothalamic prothyrotrophin-releasing hormone (proTRH) mRNA and median eminence TRH content. The effects of litter size (five or ten pups) were studied throughout lactation, while suckling-induced acute changes were analyzed on day 13 of lactation in dams with ten pups. In view of the enhanced adrenal activity during lactation and recent evidence that corticosteroids have negative effects on hypothalamic TRH, we also studied adrenalectomized (ADX) dams treated with corticosterone to maintain basal plasma corticosterone levels.
In addition to an increased plasma level of prolactin (PRL), adrenal weight and plasma corticosterone increased, while plasma TSH, tri-iodothyronine (T3), thyroxine (T4) and free T4 (FT4) levels decreased during lactation. Litter size correlated positively with plasma PRL, adrenal weight and plasma corticosterone. No effect of litter size was observed on plasma T3, but rats with ten pups had lower plasma TSH, T4 and FT4 than rats with a five-pup litter. Compared with dioestrous rats, lactating rats showed an increased hypothalamic proTRH mRNA content on day 2, but not on days 8 and 15 of lactation. Median eminence TRH in lactating rats gradually increased until day 15 and decreased thereafter. Acute suckling, after a 6-h separation of mother and pups, rapidly increased plasma PRL and corticosterone in the mothers, but had no effects on plasma TSH and thyroid hormone levels. Hypothalamic proTRH mRNA increased twofold after 0·5 h of suckling, and then gradually returned to presuckling values after 6 h. Compared with sham-operated rats, corticosterone-substituted ADX rats with ten pups had increased plasma PRL and TSH, hypothalamic proTRH mRNA and pituitary TSH β mRNA on day 15 of lactation. Moreover, while acute suckling did not enhance TSH release in sham-operated rats, it provoked not only PRL but also TSH release in corticosterone-substituted ADX dams.
It is concluded that suckling exerts a rapid, positive effect on hypothalamic proTRH mRNA content. However, the concurrent enhanced adrenal activity has negative effects on hypothalamic proTRH gene expression resulting in a suppressed hypophysial-thyroid axis during lactation. While TRH appears to play a role in PRL release during the first days of lactation and during acute suckling, TRH seems not important in maintaining PRL secretion during continued suckling.
Journal of Endocrinology (1996) 148, 325–336
Glucose tolerance and insulin secretion after adrenalectomy in mice made obese with gold thioglucose
Authors: Blair S C , Caterson I D , Cooney G J 
Published: December 2004

Abstract
The effect of adrenalectomy (ADX) on glucose tolerance and insulin secretion was examined in conscious mice made obese by a single injection of gold thioglucose (GTG). To facilitate such a study a chronic jugular catheter was implanted into the mice at the time of performing the ADX or sham-ADX. One week after ADX, the body weight (GTG-obese+sham-ADX, 35·6 ± 0·6 g; GTG-obese+ADX, 33·1 ± 0·6 g; P<0·05) and glycogen content of the liver (GTG-obese+sham-ADX, 2·4 ± 0·2 μmol/liver; GTG-obese+ADX, 1·6 ± 0·1 μmol/liver; P<0·05) of GTG-injected mice were reduced. Plasma glucose concentrations, in both the overnight fasted state and in response to an intravenous glucose load were also reduced following ADX of GTG-obese mice, but not to the level of the sham-ADX control mice. However, ADX completely normalized plasma insulin concentrations in both the basal state and also in response to a glucose load, as indicated by the finding that the integrated insulin secretory response of the ADX GTG-obese mice was not different from that of sham-ADX control mice (control+sham-ADX, 192 ± 5 min.μU/ml; GTG-obese+ADX, 196 ± 10 min.μU/ml). The effects of ADX on carbohydrate metabolism were not restricted to GTG-injected mice, as ADX of control mice decreased fasting plasma glucose levels and reduced liver glycogen and plasma insulin concentrations. The normalization of insulin release in ADX GTG-obese mice occurred while these mice were still obese and glucose intolerant. This suggests that the decreased insulin release was not due solely to an ADX-induced improvement in insulin sensitivity and/or weight loss. Removal of central glucocorticoid effects on the parasympathetic stimulation of insulin release may play a role in the reduced insulin release observed after ADX of obese and control mice, although peripheral effects of glucocorticoid deficiency on glycogen synthesis in the liver may also influence whole animal glucose homeostasis.
Journal of Endocrinology (1996) 148, 391–398
The natriuretic actions of vasopressin in the female rat: variations during the 4 days of the oestrous cycle
Authors: Forsling M L , Zhou Y , Windle R J 
Published: December 2004

Abstract
The renal actions of vasopressin were studied in the conscious female rat. Vasopressin caused a dose-dependent increase in sodium excretion when administered at 40–160 pmol/min. The highest dose, which increased sodium excretion from 10·4 ± 0·3 μmol/min (n=32) to 18·3 ± 0·8 μmol/min (n=8, P<0·001), also caused a significant rise in glomerular filtration rate (GFR). The antidiuretic and natriuretic responses to vasopressin varied significantly over the 4 days of the oestrous cycle. Both responses were greatest on pro-oestrus, being −57 ± 3 and 52 ± 3% above the control values with 80 pmol vasopressin/min. Responses of similar magnitude were also seen on dioestrus day 1. On these two cycle days the effects on urine flow and sodium excretion were accompanied by a significant increase in GFR. Smaller antidiuretic and natriuretic responses were seen on oestrus and dioestrus day 2, without concomitant changes in GFR. As the plasma vasopressin concentrations produced by hormone infusion were similar on each day of the cycle, the renal responsiveness to vasopressin appears to vary over the 4 days of the oestrous cycle. This may be important in terms of alteration and possible disturbances of fluid balance which may occur during reproductive cycles and pregnancy.
Journal of Endocrinology (1996) 148, 457–464
Changes in the immunohistochemical localisation of fibroblast growth factor-2, transforming growth factor-β1 and thrombospondin-1 are associated with early angiogenic events in the hyperplastic rat thyroid
Authors: Patel V A , Hill D J , Eggo M C , Sheppard M C , Becks G P , Logan A 
Published: December 2004

Abstract
Administration of a goitrogen (methimazole) and a low iodine diet to rats over a two-week period resulted in hypothyroidism and thyroid hyperplasia compared with controls (control: total serum thyroxine (T4) 66 ± 4 nmol/l, thyroid weight 5±1 mg/100 g body weight; experimental: T4 undetectable, thyroid weight 27 ± 4 mg/100 g body weight after 2 weeks of treatment; mean ± s.d., n=10). Immunohistochemistry carried out using a specific endothelial cell marker, CD31, and morphometric analysis (point counting of immunopositive cells) revealed that the progression of goitre in the rat thyroid is accompanied by an increase in capillary endothelial cell growth (neovascularisation). Fibroblast growth factor-2 (FGF-2) immunohistochemistry revealed widespread staining for the protein in the follicular cells of control glands. Less intense staining was found in the stroma and follicular cell nuclei. During hyperplasia and subsequent neovascularisation there was a progressive increase in the FGF-2 immunoreactivity at all locations during the two-week treatment period. Thrombospondin-1 (TSP1) immunoreactivity in the control rat thyroid was found in the stroma and in the endothelial cells, while weak follicular cell staining was also present. In the goitrous rat thyroid the TSP1 immunoreactivity was present after 1 week of treatment in the endothelial cells and most follicular cells, whilst stromal localisation was weak. After week 2 of treatment the endothelial cell and stromal localisation was no longer apparent, although a follicular localisation was still present. Transforming growth factor-β1 (TGFβ1) immunoreactivity was present in the cytoplasm of a minority of the follicular cells in control rat thyroids, while their nuclei were unstained. In the goitrous rat thyroid an increased intensity of staining for TGFβ1 was seen in all follicular cells, many of which now also demonstrated immunopositive nuclei, within one week of goitrogen administration. These results show that in the hyperplastic thyroid increases in FGF-2 and TGFβ1, and decreases in TSP1, accompany angiogenesis. These factors may interact in an autocrine/paracrine relationship to stimulate the neovascularisation that occurs during goitre formation.
Journal of Endocrinology (1996) 148, 485–499
Effect of corticosterone on protein degradation in isolated rat soleus and extensor digitorum longus muscles
Authors: Bowes S B , Jackson N C , Papachristodoulou D , Umpleby A M , Sönksen P H 
Published: December 2004

Abstract
The net catabolic effect of glucocorticoids on protein metabolism is well documented but the acute and chronic effect of glucocorticoids on protein breakdown remains controversial. In the present studies protein breakdown was measured by the release of tyrosine from the isolated soleus and extensor digitorum longus (EDL) muscles of control rats and rats treated with corticosterone (10 mg/100 g body weight/day) for 5 days.
The effect of corticosterone in arresting growth was confirmed since corticosterone-treated rats weighed significantly less than control rats after 2, 3, 4 and 5 days of treatment (P<0·001). Furthermore, the weights of soleus and EDL muscles from corticosterone-treated rats were significantly reduced (P<0·001, at least P<0·05 respectively) compared with muscles from control rats on days 3–5.
In the EDL muscle tyrosine release was significantly elevated after corticosterone treatment for 2 days (257 ± 21 nmol/g tissue/h, P<0·05), 3 days (205 ± 9 nmol/g tissue/h, P<0·01), 4 days (255 ± 20 nmol/g tissue/h, P<0·005) and 5 days (218 ± 8 nmol/g tissue/h, P<0·05) compared with EDL from control rats (192 ± 13, 171 ± 7, 187 ± 7, 180 ± 12 nmol/g tissue/h respectively). In the soleus muscle, tyrosine release was significantly elevated after corticosterone treatment for 2 days (226 ± 14 nmol/g tissue/h, P<0·001), 3 days (223 ± 16 nmol/g tissue/h, P<0·001) and 4 days (199 ± 10 nmol/g tissue/h, P<0·001) compared with control rats (158 ± 7, 132 ± 6 and 153 ± 7 nmol/g tissue/h respectively). After 5 days there was no significant difference in tyrosine release from soleus muscle between corticosterone-treated (176 ± 15 nmol/g tissue/h) and control rats (157 ± 6 nmol/g tissue/h). Plasma glucose concentrations were not significantly different in rats treated with corticosterone and control rats whilst insulin levels were significantly raised in the corticosterone-treated rats on all days compared with control rats (P<0·05 on day 1; P<0·001 on days 2, 3, 4 and 5). It is suggested that insulin may have prevented hyperglycaemia developing in the corticosterone-treated rats. Results from these studies indicate that the acute effect of glucocorticoids is to increase muscle proteolysis but this is not maintained with longer-term treatment.
Journal of Endocrinology (1996) 148, 501–507
Regional adrenal blood flow responses to adrenocorticotropic hormone after chronic embolization of the fetal placental circulation in sheep
Authors: Carter A M , Challis J R G , Svendsen P 
Published: December 2004

Abstract
To ascertain whether repeated hypoxic stress would alter the response of the adrenal cortex to adrenocorticotropic hormone (ACTH), by premature activation of the hypothalamic–pituitary–adrenal axis, we studied fetal sheep subjected to daily reduction of arterial oxygen content by embolization of the fetal placental circulation with 15 μm microspheres for 8 days from about day 124 of gestation (term ∼147 days) and sham-embolized controls. Starting before the final embolization (or shamembolization) on day 8, and continuing for 24 h, the fetus was given an intravenous infusion of ACTH1–24 (0·5 μg/h) or vehicle. Fetal and maternal blood samples were taken for determination of immunoreactive cortisol, and regional adrenal and fetal placental blood flows were measured by the microsphere technique at three time points: 1 h before infusion, 3 h after the start of the infusion (1 h after embolization), and after 24 h of infusion. Prior to infusion of ACTH or vehicle, fetal placental blood flow was lower in microsphere-embolized fetuses than in sham-embolized controls (199 ± 15 vs 292 ± 25 ml/min per 100 g tissue; mean ± s.e.; P<0·01). However, plasma cortisol and adrenal cortical blood flow did not differ between embolized fetuses and controls. Adrenal vascular responses to the 24-h infusion of ACTH were similar in embolized and shamembolized fetuses. Adrenal cortical blood flow increased 3-fold (P<0·05) due to decreased vascular resistance (P<0·01), with no change in adrenal medullary blood flow. Thus, while daily embolization of the fetal placental circulation caused a sustained decrease in cotyledonary blood flow, no evidence of altered responsiveness of the adrenal cortex to ACTH was found in these experiments.
Journal of Endocrinology (1996) 148, 517–522
Expression of α2- and β-adrenoceptor subtypes in human islets of Langerhans
Authors: Lacey R J , Chan S L F , Cable H C , James R F L , Perret C W , Scarpello J H B , Morgan N G 
Published: December 2004

Abstract
Sequences from cDNA molecules encoding α2-adrenoceptor subtype genes were subcloned into prokaryotic vectors and riboprobes generated to hybridise selectively with each of the human α2C2-, α2C4- and α2C10-adrenoceptor subtype mRNA species. The riboprobes were labelled with either 32P or digoxigenin and used to study the expression of α2-adrenoceptor subtypes in sections of human pancreas, in isolated human islets of Langerhans and in clonal HIT-T15 pancreatic β-cells. Using a ribonuclease protection assay protocol, expression of mRNA species encoding both α2C2 and α2C10 was demonstrated in preparations of isolated human islets of Langerhans. mRNA encoding α2C4 was also detected in human islet RNA, using reverse transcription coupled with the polymerase chain reaction. In situ hybridisation was then employed to examine the distribution of each α2-adrenoceptor subtype in sections of human pancreas. All three subtypes of α2-adrenoceptor mRNA were identified in sections of formalin-fixed, paraffinembedded human pancreas using riboprobes labelled with digoxigenin. Although some labelling of the three α2-adrenoceptor mRNA subtypes was seen in the islets, the labelling was most intense in the exocrine tissue of the pancreas for each receptor subtype. The specificity of the digoxigenin-labelled RNA probes was confirmed in several control tissues and by in situ hybridisation studies using sense probes in the pancreas. The integrity of the pancreas sections was confirmed by in situ hybridisation with an antisense riboprobe derived from human insulin cDNA. The results demonstrate that multiple α2-adrenoceptor subtypes are expressed in human pancreas. Both the exocrine and endocrine cells express more than one receptor subtype, although the islets stain less intensely than the bulk of the tissue suggesting that the islet cells may have lower levels of expression than the acinar tissue. The presence of α2-adrenoceptor subtype mRNA species in pancreatic β-cells was confirmed by Northern blotting of RNA extracted from the clonal β-cell line, HIT-T15. Transcripts encoding each of the three cloned α2-adrenoceptor subtypes were detected in HIT-T15 cells.
Hybridisation of sections of human pancreas with oligodeoxynucleotide probes designed to hybridise with β2-adrenoceptor mRNA revealed expression of this species in islet β-cells but not in the exocrine tissue of the pancreas.
Journal of Endocrinology (1996) 148, 531–543