bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stimulation of cortisol production in isolated bovine zona fasciculata cells by phorbol ester: role of ion fluxes
Authors: Kenyon C. J. , Anyaorah L. , Woodburn L. , Connell J. M. C. , Fraser R. 
Published: December 2008

ABSTRACT
The role of protein kinase C activation in the control of cortisol synthesis was studied using the phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA). Bovine zona fasciculata cells were incubated with various concentrations of TPA in the presence and absence of EGTA, verapamil or nitrendipine to see whether cortisol stimulation was dependent on extracellular calcium ions. When free extracellular concentration of Ca2+ was reduced to approximately 10 μmol/l the cortisol response at all concentrations of TPA was reduced by approximately 25% indicating that protein kinase C activation is only partially dependent on extracellular calcium ions. This is confirmed by the effects of the voltage-dependant calcium channel blocker verapamil, which partially inhibited the cortisol response to a maximally effective concentration of TPA (1 μmol/l). However, a second channel blocker, nitrendipine, proved to be ten times more potent than verapamil and totally inhibited the TPA response. The partial effects of EGTA and verapamil and the contrast between verapamil and nitrendipine do not exclude the possibility that intracellular calcium ions are important in protein kinase C activation and may indicate that nitrendipine has better access to an additional site of inhibitory action than verapamil. It is significant that the ionophore A23187, which facilitates Ca2+ entry independently of voltage-sensitive channels, failed to overcome the inhibitory effects of nitrendipine in TPA-stimulated cells.
In some other tissues, the effects of protein kinase C activation are mediated by the opening of Na+/H+ exchange ports. The involvement of this port in the cortisol response has been tested by incubating TAP-and ACTH-treated cells with amiloride, an inhibitor of Na+/H+ exchange. It would seem unlikely that the steroidogenic effects of TPA are mediated by altered Na+/H+ exchange because, at the high concentration of amiloride used to block cortisol synthesis (1 mmol/l), non-specific side effects may occur and also because amiloride at this concentration inhibited the cortisol response to ACTH whose mechanism of action is not solely dependent on protein kinase C activation.
Cells were also incubated with increasing concentration of TPA in the presence and absence of ACTH and angiotensin. TPA did not further stimulate ACTH-treated cells and at 0·32 μmol/l inhibited cortisol synthesis. The effects of angiotensin and TPA were additive which suggests that the steroidogenic effects of angiotensin II are largely independent of protein kinase C activation.
J. Endocr. (1988) 117, 423–429
Effect of difluoromethylornithine on the LH surge and subsequent ovulation in the rat
Authors: Nicholson S. A. , Aslam M. , Chuang T. T. , Gillham B. , Jones M. T. 
Published: December 2008

ABSTRACT
Female Wistar-derived rats with regular oestrous cycles were injected s.c. at 15.00 h on pro-oestrus with difluoromethylornithine (DFMO), a specific inhibitor of ornithine decarboxylase. The drug (10–100 mg/rat) caused a dose-related reduction in the concentration of LH in plasma taken at 19.00 h (the time of the peak of the LH surge in this colony). There was also a dose-related reduction in the pituitary content of total polyamines. The reduction in the plasma concentration of LH was not due to the shifting of the time of the peak of the surge, as concentrations were significantly lower than control from 17.00 to 21.00 h, the overall reduction in total LH release being approximately 50%. The number of ova in the oviducts at 06.00 h next morning was significantly reduced by treatment with 50 mg DFMO/rat, by an average of 70%.
Injection of DFMO enhanced the fall in plasma oestradiol concentrations seen between 15.00 and 19.00 h, in a dose-related manner. It also prevented the rise in progesterone concentrations seen in control animals during this period. The ability of DFMO to prevent the rise in plasma concentrations of LH was not secondary to the effects of the drug on ovarian steroid production because DFMO also significantly reduced the LH surge in animals ovariectomized on dioestrus and given appropriate replacement injections of oestradiol and progesterone.
It seems possible that part of the action of DFMO is exercised at the hypothalamus, since when 50 mg DFMO/rat was given either 2 or 4 h before the expected peak of the LH surge, the LHRH content of the hypothalamus was significantly reduced at that time. These results suggest that activation of ornithine decarboxylase is a necessary prerequisite for a normal LH surge, and that this activation is steroid-dependent. This conclusion is borne out by results from direct observations on the activity of the enzyme in pituitary tissue incubated in vitro.
J. Endocr. (1988) 117, 447–453
The natural history of adrenal function in autoimmune patients with adrenal autoantibodies
Authors: Betterle C. , Scalici C. , Presotto F. , Pedini B. , Moro L. , Rigon F. , Mantero F. 
Published: December 2008

ABSTRACT
Adrenal autoantibodies (AA) were found in 23 of 2571 (0·9%) patients with organ-specific autoimmune diseases, in one of 632 first-degree relatives of insulin-dependent diabetic patients, and in none of 375 normal controls. In AA-positive subjects the prevalence of human leucocyte antigens (HLA)-A1, -B8 and -DR3 was significantly higher with respect to the general population. Two groups were followed (15 subjects persistently positive for AA and 51 negative subjects) for a mean period of 3·2 years. Yearly tests were made for AA and adrenal function. Of the 15 subjects persistently positive for AA, six developed Addison's disease after a period varying from 6 months to 10 years. Of the 51 subjects initially negative, two became positive during follow-up, and one of these developed Addison's disease 16 months later. In contrast, all the remaining 49 persistently negative subjects maintained normal adrenal function tests. Overall, of the 17 positive subjects, seven (41%) developed Addison's disease, three (18%) showed various degrees of subclinical adrenocortical failure and the remaining seven maintained normal glandular function. In the positive patients the yearly incidence of detriment in adrenal function was 19%. Patients who developed Addison's disease showed significant association with HLA-B8 phenotype. The development from normal adrenocortical function to overt Addison's disease seemed to progress through four distinct stages of functional impairment: increased plasma renin activity with normal/low aldosterone (stage 1), low cortisol response after i.v. administration of ACTH (stage 2), increased ACTH (stage 3), and low basal cortisol (stage 4). Thus, idiopathic Addison's disease appears to be a chronic autoimmune disorder with a genetic predisposition and a long preclinical period marked by the presence of AA. Steroid-producing cell antibodies were also evaluated but they were not found to be markers of gonadal dysfunction.
J. Endocr. (1988) 117, 467–475
The isolation, purification and some properties of pheromaxein, the pheromonal steroid-binding protein, in porcine submaxillary glands and saliva
Authors: Booth W. D. , White C. A. 
Published: December 2008

ABSTRACT
Pheromaxein, the 16-androstene steroid-binding protein with a relative molecular mass of 15 000 was isolated in sub-milligram quantities from the submaxillary gland and saliva of the Gottingen miniature boar, after a fourfold purification involving the following methods: ultrafiltration for submaxillary gland cytosols and ethanol precipitation for saliva, Concanavalin-A-Sepharose affinity chromatography, sodium dodecyl sulphate polyacrylamide gel electrophoresis, 'Extractigel-D' affinity chromatography (to remove sodium dodecyl sulphate) and fast protein-liquid chromatography. Yields of purified pheromaxein obtained after fast protein-liquid chromatography represented 10–20% of total protein present in an ultrafiltrate of a submaxillary gland cytosol. Fast protein-liquid chromatography separated the α- and β-charge isomers of pheromaxein which were shown to have isoelectric points of 4·78 and 5·35 respectively on flat-bed isoelectric focusing. Some data are provided for the variable occurrence of the isomeric forms of pheromaxein in relation to different breeds of pig. Five 16-unsaturated steroids showed the highest binding to pheromaxein. Other steroids of the 5α- and 5β-androstane series also showed some binding to pheromaxein, i.e. 17β-hydroxy-5α-androstan-3-one (19·2%), with 5α-androstan-3-one, which has a similar urinous odour to 5α-androst-16-en-3-one, showing the greatest binding (42·6%) relative to 5α-androst-16-en-3-one (100%).
J. Endocr. (1988) 118, 47–57
Early changes in serum concentrations of somatomedin-C induced by dietary protein deprivation in rats: contributions of growth hormone receptor and post-receptor defects
Authors: Maiter D. , Maes M. , Underwood L. E. , Fliesen T. , Gerard G. , Ketelslegers J.-M. 
Published: December 2008

ABSTRACT
To define the mechanism(s) for the decrease of somatomedin concentrations in acute protein malnutrition, we have assessed the relationships between serum immunoreactive somatomedin-C/insulin-like growth factor-I (Sm-C/IGF-I), serum immunoreactive GH and total (MgCl2-treated homogenates) as well as free (water-treated homogenates) liver somatogenic (GH) binding sites in growing rats fed a 5% protein diet for 12 or 24 h and given an s.c. injection(s) of rat GH (rGH) or saline. Control rats were fed a 15% protein diet and injected with rGH or saline.
After 12 and 24 h of protein restriction, body weight was 6·9 and 8·2% below controls respectively (P < 0·001), while Sm-C/IGF-I concentrations were reduced by 58 and 66% respectively (P < 0·001 vs controls). Serum GH concentrations were not affected by the low protein intake. Furthermore, injection(s) of 50–100 μg rGH failed to raise serum Sm-C/IGF-I concentrations in the protein-deficient animals. The number of total and free GH-binding sites was modestly (15–20%) decreased at 12 and 24 h in the protein-restricted rats. Serum Sm-C/IGF-I concentrations correlated weakly with free and total binding sites (r = 0·48 and 0·38 respectively). Affinity constants of GH-binding sites were not changed by protein restriction.
The profound reduction in Sm-C/IGF-I concentrations within a few hours of beginning protein restriction, and the discordance between this reduction and the small decline in somatogenic binding sites, suggests that, in addition to GH receptor loss, a postreceptor defect may participate in the GH resistance occurring in the early stages of protein deficiency.
J. Endocr. (1988) 118, 113–120
Effect of the suckling stimulus on daily LH surges induced by chronic oestrogen treatment in ovariectomized lactating rats
Authors: Tsukamura H. , Maeda K.-I. , Yokoyama A. 
Published: December 2008

ABSTRACT
Effects of the suckling stimulus on the daily LH surge induced by chronic oestrogen treatment were examined in ovariectomized lactating rats. Wistar– Imamichi strain rats were kept under 14 h light:10 h darkness (lights on at 05.00 h). Litter size was adjusted to eight on day 1 (day 0 = day of parturition) and ovariectomy performed on day 2. Lactating rats deprived of their litters on day 0 served as non-lactating controls. Silicone elastomer tubing filled with oestradiol was implanted on day 6 or 15. Blood samples were collected through an indwelling cannula at 10.00 and 17.00 h on each day after implantation to detect daily LH surges. Daily LH surges occurred in the late afternoon in both lactating and non-lactating rats implanted with oestradiol on day 6 or 15. The amplitude of daily LH surges in lactating rats implanted on day 6 declined much more rapidly than in non-lactating rats implanted on day 6, but no significant difference was found in the profile of the LH surge between lactating and non-lactating rats implanted on day 15. Pituitary LH contents just before the daily LH surge (12.00–12.30 h) 4 days after implantation in lactating rats implanted with oestradiol on day 6 were significantly less than those in non-lactating rats implanted with oestradiol on day 6 or 15 and in lactating rats implanted on day 15. These results suggest that the mechanisms responsible for the oestradiol-induced LH surge were not impaired by the suckling stimulus, and that a rapid decline of the amplitude of LH surges observed in mid-lactation could be ascribed to the small amount of LH stored in the pituitary.
J. Endocr. (1988) 118, 311–316
Adrenal glands alter the concentration of oestradiol-17β and its receptor in the uterus of ovariectomized ewes
Authors: Atkinson S. , Adams N. R. 
Published: December 2008

ABSTRACT
To investigate the effects of adrenal hormones on oestrogen activity in the uterus, ovariectomized ewes were either adrenalectomized, administered glucocorticoid-like preparations (CORT), or remained as controls. The adrenalectomized ewes were maintained with a corticoid-replacement therapy and monitored daily for plasma glucose and Na+/K+ concentrations. Blood samples were collected from all ewes at 15-min intervals for 4 h and assayed for LH and FSH. The adrenalectomized ewes were killed 9 days after adrenalectomy, while the CORT ewes were killed after 3 weeks of drug therapy. The control ewes were killed simultaneously with the CORT ewes. Uterine tissues were homogenized and the numbers of oestradiol receptors and tissue concentrations of oestradiol-17β were measured. The adrenalectomized ewes had significantly higher concentrations of cytosolic oestrogen receptors in the uterus than did the control ewes, which had significantly higher concentrations than the CORT ewes (0·95±0·06, 0·76 ± 0·02 and 0·60±0·02 (s.e.m.) μmol/kg protein respectively). The concentrations of oestradiol-17β measured in uterine tissues were significantly lower in adrenalectomized and CORT ewes than in control ewes (37·4±5·5, 61·7±25·7 and 135·5 ± 12·8 pmol/kg respectively). There were no significant differences between any groups in the peripheral concentrations of LH or FSH. These results indicate that the adrenal gland affects the concentrations of both oestrogen and its receptor in the uterus of ovariectomized ewes, probably by different mechanisms. These effects are not mediated by gonadotrophins.
J. Endocr. (1988) 118, 375–380
The influence of plasma concentrations of tri-iodothyronine on the acute increases in insulin and muscle protein synthesis in the refed fasted rat
Authors: Millward D. J. , Brown J. G. , van Bueren J. 
Published: December 2008

ABSTRACT
To examine whether the low plasma levels of triiodothyronine (T3) in fasted rats might limit the recovery of muscle protein synthesis on refeeding, rats were fasted for either 3 or 4 days and refed with or without pretreatment with thyroid hormones. Fasting suppressed T3 levels, plasma insulin and the rate of the translational phase of muscle protein synthesis (KRNA; the rate per unit RNA), especially after the 4-day fast. On refeeding, plasma T3 levels remained low for more than 3 h after the 3-day fast and for more than 8 h after the 4-day fast. Insulin concentrations increased within the first hour of refeeding, eventually achieving supranormal concentrations after the 3-day fast. The KRNA increased within the first hour of refeeding, achieving well-fed control values by 3 h after the 3-day fast or 24 h after the 4-day fast. The increases in KRNA were significantly correlated with the increases in insulin at low insulin concentrations, achieving a plateau value at 150 pmol/l, so that further increases in insulin were not associated with any further increases in protein synthesis. Pretreatment with thyroid hormone induced increased T3 levels which were maintained for up to 8 h of refeeding. This had no effect on the responses of either insulin or protein synthesis to refeeding after the 3-day fast, but did result in an acceleration of the recovery in the KRNA and plasma insulin levels in the rats fasted for 4 days. Analysis of the insulin–KRNA relationship showed no evidence for any increase in the insulin sensitivity of muscle protein synthesis with thyroid pretreatment, the initial stimulation of protein synthesis on refeeding the rats fasted for 4 days reflecting increased insulin secretion. Since in the untreated animals, insulin secretion on refeeding was also correlated with T3 levels, these results are consistent with the previously reported thyroidal dependence of insulin secretion.
J. Endocr. (1988) 118, 417–422
Regulation of aldosterone secretion by avian adrenocortical cells
Authors: Rosenberg J. , Pines M. , Hurwitz S. 
Published: December 2008

ABSTRACT
Dispersed chick adrenocortical cells were incubated with mammalian and avian angiotensin-II, Ca2+, K+, verapamil, nifedipine, Ca2+ ionophore (A23187), protein kinase-C activator (phorbol 12-myristate 13-acetate; TPA), atrial natriuretic peptide (ANP), sodium nitroprusside (SNP) and ACTH. Secretion of aldosterone and corticosterone, and accumulation of cyclic nucleotides were assessed.
Secretion of aldosterone was not affected by angiotensin-II, Ca2+ channel blockers, Ca2+ ionophore or TPA. ANP stimulated production of cyclic GMP (cGMP), and inhibited aldosterone secretion with a similar dose–response relationship. SNP also stimulated cGMP production and inhibited the ACTH-stimulated aldosterone secretion. The results indicate that ANP is an inhibitor of aldosterone secretion in birds and suggest that this inhibition is mediated by cGMP. In contrast to mammalian glomerulosa cells, angiotensin-II and the calcium-inositol phosphate-protein kinase C pathway appear not to be involved in the regulation of aldosterone secretion by avian adrenal cells.
J. Endocr. (1988) 118, 447–453
Long-term effects of a gonadotrophin-releasing hormone agonist ([d-Ser(But)6]GnRH(1–9)nonapeptide-ethylamide) on gonadotrophin secretion from human pituitary gonadotroph cell adenomas in vitro
Authors: Daniels M. , Newland P. , Dunn J. , Kendall-Taylor P. , White M. C. 
Published: December 2008

ABSTRACT
We have studied the effects of TRH and native gonadotrophin-releasing hormone (GnRH), and of a GnRH agonist (Buserelin; [d-Ser(But)6]GnRH(1–9) nonapeptide-ethylamide), on LH, FSH, α subunit and LH-β subunit secretion from three human gonadotrophin-secreting pituitary adenomas in dispersed cell culture. During a 24 h study, treatment with 276 nmol TRH/1 resulted in a significant (P < 0·05) stimulated release of FSH and α subunit from all three adenomas, and LH from the two adenomas secreting detectable concentrations of this glycoprotein; treatment with 85 nmol GnRH/l significantly (P < 0·05) stimulated the release of α subunit from all three, but FSH from only two and LH from only one adenoma. During a long-term 28-day study, basal FSH and α subunit concentrations were maintained, but secretion of LH, and LH-β (detectable from one tumour only), declined with time from two of the three adenomas. Addition of Buserelin to the cultures resulted in the continuous (P < 0·05) stimulation of α subunit secretion from all three adenomas, and of LH and FSH from two, whilst a transient stimulatory effect on LH and FSH secretion was seen from a third adenoma, with subsequent secretion rates declining towards control values. These data show that human gonadotrophin-secreting adenomas demonstrate variable stimulatory responses to hypothalamic TRH and GnRH, and that during chronic treatment with a GnRH agonist the anticipated desensitizing effect of the drug was not observed in two out of three adenomas studied. The mechanism for this is not clear, but such drugs are unlikely to be of therapeutic value in the management of gonadotrophin-secreting tumours. The data also suggest that GnRH and GnRH agonists have a differential effect on the in-vitro release of intact gonadotrophins and the common α subunit.
J. Endocr. (1988) 118, 491–496
Leukotriene release by human fetal membranes, placenta and decidua in relation to parturition
Authors: Rees M. C. P. , Di Marzo V. , Bernal A. Lopez , Tippins J. R. , Morris H. R. , Turnbull A. C. 
Published: December 2008

ABSTRACT
Complete placentas and membranes were obtained from women after uncomplicated singleton pregnancies. Six were collected after labour at term, six after preterm labour and six after elective Caesarean section at term. Leukotriene C4 (LTC4), leukotriene D4 (LTD4) and leukotriene E4 (LTE4) release was examined using a short-term incubation technique. Release by amnion was significantly higher than that by the other tissues for the three modes of delivery. Comparison of LTC4, LTD4 and LTE4 release by individual tissues with regard to the type of delivery showed no significant difference.
J. Endocr. (1988) 118, 497–500
Intra- and extravascular turnover of thyrotrophin-releasing hormone in normal man
Authors: Iversen E. 
Published: December 2008

ABSTRACT
In 14 normal subjects constant TRH infusions for determination of plasma clearance rate (PCR) and half-life of disappearance (t½) of TRH were carried out with simultaneous determination of half-life of disappearance of TRH in serum in vitro (t½p). PCR, t½ and t½p were 1532 ± 423 ml/min, 6·6 ± 1·5 min and 16·8 ± 9·4 min respectively (mean ± s.d.) and displayed only minor fluctuations when determined repeatedly in the same subjects (coefficients of variation within individuals were 15·1, 10·6 and 7·5% respectively). Simultaneous determination of PCR, t½ and t½p enabled calculation of the half-life of disappearance of TRH in the extravascular tissue compartment (t½t). Values of t½t (6·3 ± 1·4 min) correlated to t½p (r = 0·95). Activities of TRH-degrading enzymes in tissues and in serum were independent of sex, phase of female menstrual cycle, time of day and of the concentrations of TRH used. The methods employed for this investigation offer the possibility of examining the degradation of TRH and TRH analogues both in the serum and in the extravascular compartment during various conditions.
J. Endocr. (1988) 118, 511–516
SECRETION OF β-ENDORPHIN INTO THE MATERNAL CIRCULATION BY UTEROPLACENTAL TISSUES IN RESPONSE TO HYPOGLYCAEMIC STRESS
Authors: Falconer J. , Chan E.-C. , Madsen G. , Thomson M. , Davies J. , Smith R. 
Published: December 2008

ABSTRACT
The placenta has been shown to contain ACTH and β-endorphin but the roles of these peptides are unknown. To investigate whether they are released into the maternal circulation from the placenta in response to physiological stimuli the effects of hypoglycaemic stress were investigated. Plasma samples were collected from the femoral artery (FA) and uterovarian (UV) vein of nine pregnant sheep before and during hypoglycaemia induced by intravenous insulin (100U). Plasma concentrations of ovine β-endorphin (oβ-EP) were measured by radioimmunoassay. Concentrations of oβ-EP rose in both vessels by 60 min after insulin. The peak concentrations of oβ-EP (pmol/l) were 122 ± 29 (mean ± SEM, n=8) in the UV and 96±24 (n=9) fmol/ml in the FA 60 min after insulin injection. There was no difference between the concentrations of oβ-EP in the vessels before insulin injection but at 60 and 120 min after insulin the concentrations of oβ-EP were significantly higher in the UV than FA (P<0.02, analysis of variance). This indicates that the pregnant uterus or placenta can respond to hypoglycaemia by secreting β-EP into the maternal circulation. It is therefore possible that placental pro-opiomelanocortin (POMC) peptides may have a role in maternal endocrinology and metabolism.