bluuebunny/crossref_metadata_2025_split huggingface dataset:
The glucocorticoid antagonist mifepristone reveals abnormal regulation of the adrenocortical system in obese Zucker rats
Authors: Pesonen U. , Koulu M. , Heikinheimo O. , Huupponen R. 
Published: December 2008

ABSTRACT
The effects of the potent glucocorticoid type-II receptor (GR) antagonist, mifepristone, on corticosterone secretion and on expression of preprocorticotrophin-releasing factor (preproCRF) mRNA in the hypothalamic paraventricular nucleus (PVN) and of pro-opiomelanocortin (POMC) mRNA in the pituitary gland were investigated in lean and obese Zucker rats. Treatment with mifepristone for 4 days (10 mg/kg orally twice daily) significantly (P < 0·05) stimulated corticosterone secretion in lean but not in obese rats. In lean rats the enhanced corticosterone secretion was associated with non-significant increments in the expression of preproCRF mRNA in the PVN and of POMC mRNA in the pituitary gland, while mifepristone significantly (P < 0·05) reduced the expression of preproCRF mRNA in the PVN of obese Zucker rats. It is concluded that antagonism of GR by mifepristone results in persistent activation of the adrenocortical axis in lean Zucker rats due to blockade of feedback inhibition by circulating corticosterone. In obese animals the abnormal response to mifepristone suggests that the neuroendocrine control of the HPA axis is altered in genetically determined obesity.
Journal of Endocrinology (1992) 132, 425–431
Osteoclast formation together with interleukin-6 production in mouse long bones is increased by insulin-like growth factor-I
Authors: Slootweg M. C. , Most W. W. , van Beek E. , Schot L. P. C. , Papapoulos S. E. , Löwik C. W. G. M. 
Published: December 2008

ABSTRACT
Insulin-like growth factor-I (IGF-I) is a potent stimulator of bone formation. Whether this growth factor also induces bone resorption has not been studied in detail. We used two organ culture systems to examine the direct effect of IGF-I on bone resorption. Fetal mouse radii/ulnae, containing mature osteoclasts, showed no response to IGF-I, indicating that osteoclastic activity is not influenced by IGF-I. Fetal mouse metacarpals/metatarsals, containing just osteoclast precursors and progenitors, showed an increase in resorption in response to IGF-I, indicating that IGF-I stimulates the formulation of osteoclast precursors/progenitors and thereby increases the number of osteoclasts.
Interleukin-6 (IL-6) has been hypothesized to be a mediator of bone resorptive agents such as parathyroid hormone (PTH). Both radii/ulnae and metacarpals/metatarsals reacted to IGF-I with an increase in IL-6 production. IL-6 production by UMR-106 osteogenic osteosarcoma cells was positively modulated by IGF-I, indicating that osteoblasts are likely to be the cells responsible for increased IL-6 production by the bones, and that IL-6 might be a mediatory of IGF-I-stimulated bone resorption.
Journal of Endocrinology (1992) 132, 433–438
Further characterization of the steroidogenic responsiveness of purified zona fasciculata/reticularis cells from bovine adrenal cortex before and after primary culture: changing responsiveness to phosphoinositidase C agonists
Authors: Bird I. M. , Clyne C. D. , Lightly E. R. T. , Williams B. C. , Walker S. W. 
Published: December 2008

ABSTRACT
When bovine adrenocortical cells from the zona fasciculata/reticularis (zfr) are maintained in primary culture, cortisol secretion in response to acute stimulation with ACTH and adrenaline (which activate adenylate cyclase) is seen to increase steadily over the first 48 h, while secretion in response to angiotensin II and acetylcholine (which activate phosphoinositidase C) shows an initial decline in the first 24 h and a recovery to maximum after 48 h. We have investigated whether these discrepant changes in cortisol secretory response to the different agonists are due to changes in formation of the associated second messengers (cAMP or inositol phosphates), or altered coupling of these second messenger signals to steroid secretion.
Increases in steroid secretion in response to ACTH and adrenaline were paralleled by increased cAMP. Steroid secretion in response to exogenous 8-bromoadenosine 3′:5′-cyclic monophosphate also increased steadily during this 48-h period. Thus increased responsiveness was due to both increased second messenger formation and increased coupling to the steroid secretory response.
The decreased steroid secretory response to angiotensin and acetylcholine after 24 h, and subsequent recovery after 48 h in culture, were accompanied by an increased formation of phosphoinositols after 24 h and a further increase by 48 h. However, the steroid secretory response to a combination of calcium ionophore and the protein kinase C activator, phorbol 12-myristate 13-acetate, was reduced after 24 h and recovered by 48 h of culture. Fura-2-loaded cells also showed an increase in intracellular [Ca2+] after 24 h in culture. Thus the impaired steroid secretory response to angiotensin II and acetylcholine after 24 h of culture was not due to reduced formation of second messengers but to a failure of Ca2+ and diacylglycerol so formed to activate the steroid secretory process.
Reversible uncoupling of the steroid secretory response from the Ca2+- and diacylglycerol-based but not the cAMP-based second messengers observed in bovine zfr cells suggests that differential control of steroid secretion and other cell functions may be possible in vivo for activators of phosphoinositidase C, and may explain apparently discrepant results from studies on other in-vitro adrenocortical cell preparations.
Journal of Endocrinology (1992) 133, 21–28
Effect of administration of growth hormone on plasma and intracellular levels of thyroxine and tri-iodothyronine in thyroidectomized thyroxine-treated rats
Authors: Geelhoed-Duijvestijn P. H. L. M. , Roelfsema F. , Schröder-van der Elst J. P. , van Doorn J. , van der Heide D. 
Published: December 2008

ABSTRACT
We have studied the effects of the administration of GH on plasma levels and peripheral production of tri-iodothyronine (T3) from thyroxine (T4) in thyroidectomized male Wistar rats given a continuous i.v. infusion of T4 (1 μg/100 g body weight per day) and GH (120 μg per day) for 3 weeks. Tracer doses of 131I-labelled T3 and 125I-labelled T4 were added to the infusion. At isotopic equilibrium (10 days after the addition of 125I-labelled T4) the rats were bled and perfused.
The plasma appearance rate for T3 was higher (10·6±1·3 vs 8·4 ± 2·8 pmol/h per 100 g body weight, P = 0·05) and plasma TSH was lower (246±24 vs 470±135 pmol/l, P<0·01) in GH-treated rats. The amount of T3 in liver (12·3 ±2·8 vs 5·5 ± 1·7 pmol/g wet weight, P<0·01), kidney (11·5±1·4 vs 6·5± 1·4 pmol/g wet weight, P <0·01) and pituitary (8·8 ±2·7 vs 4·8±0·5 pmol/g wet weight, P< 0·01) was higher than in controls, mainly as a result of an increased local production of T3 from T4, but plasma-derived T3 was also higher in most organs.
We found an increased intracellular T3 concentration in the pituitary which may be responsible for the lower plasma TSH concentration in the GH-treated rats. Since the increase in locally produced T3 is found particularly in liver, kidney and pituitary, typical organs that express 5′-deiodinase activity, we suggest that GH acts on thyroid hormone metabolism by stimulating type-I deiodinase activity.
Journal of Endocrinology (1992) 133, 45–49
Kinetics of placental lactogen in mid- and late-gestation ovine fetuses
Authors: Schoknecht P. A. , Currie W. B. , Bell A. W. 
Published: December 2008

ABSTRACT
Placental lactogen (PL) is found in fetal plasma throughout gestation, and PL receptors occur on many types of fetal cells. In this study, the entry rate of PL into the fetal circulation was estimated by injection of 125I-labelled ovine PL into two mid- and four late-gestation fetuses. At both ages, PL appears to be distributed into two body pools. One pool has a rapid half-life (approximately 9 min) and a volume of distribution approximately 8% of body weight, while the second pool has a longer half-life (approximately 45 min) and a distribution volume only 4% of body weight. The first pool is presumably blood plasma, but the physiological identity of the second pool is unknown. The effective half-life of PL is approximately 15 min, and the liver is suggested as a probable major site of degradation. These estimates were confirmed in late gestation by measuring fetal plasma concentrations of PL in response to a continuous infusion of unlabelled PL. The kinetic parameters estimated in this study can be used to determine the quantity of exogenous hormone required to alter PL concentration in fetal plasma in a predictable manner.
Journal of Endocrinology (1992) 133, 95–100
Cultured dermal papilla cells from androgen-dependent human hair follicles (e.g. beard) contain more androgen receptors than those from non-balding areas of scalp
Authors: Randall V. A. , Thornton M. J. , Messenger A. G. 
Published: December 2008

ABSTRACT
Androgens stimulate hair growth in many areas, e.g. the beard; they also induce regression and balding on the scalp with increasing age in genetically disposed individuals. The cause(s) of this biological conundrum is unknown but age-related; androgen-potentiated changes also occur in the prostate. The mesenchymederived dermal papilla situated at the base of the hair follicle is thought to play an important role in regulating the growth and development of the follicular epithelium. Since androgens probably act on the hair follicle via the dermal papilla, cultures of dermal papilla cells from human hair follicles with differing responses to androgens in vivo have been established and their ability to bind androgens assessed. Receptor binding was assayed by saturation analysis (0·05–10 nmol/l) using the synthetic non-metabolizable androgen, [3H]mibolerone. Shionogi 115 cells were also assayed as a positive control.
Specific high-affinity low-capacity androgen receptors were identified in 12 dermal papilla primary cell lines with similar characteristics to established androgen receptors. Cells from androgen-sensitive follicles (beard, scrotum and pubis) contained higher levels of androgen receptors than those derived from relatively androgeninsensitive non-balding scalp follicles whether the receptor content was calculated in relation to cell number, protein or DNA content of the cells. These results support the hypothesis that androgens act on hair follicles via the dermal papilla in vivo and demonstrate that dermal papilla cells exhibit an altered phenotype in culture which depends on the body site from which they were derived. Cultured human dermal papilla cells should prove a useful model system for studies of the mechanism of androgen action, and further investigations may elucidate the paradox of why bald men can grow beards.
Journal of Endocrinology (1992) 133, 141–147
Vitamin A deficiency and glucocorticoid receptor activity in rat liver
Authors: Audouin I. , Garcin H. , Pailler-Rodde I. , Higueret P. 
Published: December 2008

ABSTRACT
The influence of vitamin A on the binding properties of hepatic glucocorticoid receptors (GR) was studied in young rats 7 weeks after they had been given a diet with or without vitamin A. Scatchard analysis showed an increased capacity of cytosolic GRs to bind dexamethasone in vitamin A deficiency. In these rats, an increase in tyrosine aminotransferase also occurred, and this could be related to the increased formation of hormone–GR complexes. Measurement of protein kinase C activity showed an increase which might be related to the functional activity of GRs.
Journal of Endocrinology (1992) 133, 169–173
A comparative analysis of the neuroendocrine mechanisms regulating ovulation, affected by a unilateral implant of atropine in the preoptic-anterior hypothalamic area, in intact and hemiovariectomized adult rats
Authors: Cruz M. E. , Castro J. , Domínguez R. 
Published: December 2008

ABSTRACT
The effects were analysed of a unilateral implant of atropine on ovulation in intact and hemiovariectomized adult rats, together with the response of the atropine-implanted rats to hormone replacement. An outer cannula directed to the left or right preoptic (POA)-anterior-hypothalamic area (AHA) was implanted into cyclic adult rats. A group of animals in oestrus was hemiovariectomized and some were also implanted with a cannula. After two consecutive 4-day cycles, the hemiovariectomized animals were implanted with atropine (23 ± 4 μg) or cholesterol (25 ± 2 μg) on the day of oestrus. Atropine implanted into the left side of the POA-AHA blocked ovulation and compensatory ovarian hypertrophy, whilst implants in the right side had no effects. Administration of gonadotrophin-releasing hormone (GnRH; 3·7 μg/kg) at 13.00 h on the expected day of pro-oestrus induced ovulation in six out of seven treated animals. Of 19 rats with an implant of atropine in the left side of the POA-AHA, one ovulated after treatment with pregnant mare serum gonadotrophin (PMSG) on oestrus, or oestradiol benzoate or human chorionic gonadotrophin (hCG) on day 2 of dioestrus. The effects on ovulation of a unilateral implant of atropine into the POA-AHA of cyclic adult rats and the responses of such rats to GnRH, PMSG, hCG and oestradiol benzoate replacement were also studied. Ovulation was induced in rats with a unilateral implant of atropine and which had been treated with GnRH or hCG at 13.00 h on the expected day of pro-oestrus after the implant. In rats with an atropine implant, treatment with PMSG on the day of implantation or with oestradiol benzoate on day 2 of dioestrus restored ovulation in those with the implant in the left side of the hypothalamus, but was ineffective in those with the implant in the right side. The results suggested that in the adult rat the muscarinic mechanisms regulating preovulatory GnRH release, as well as the stimulatory effects of oestrogen, are lateralized. As the results observed in intact and hemiovariectomized animals subjected to the same treatments were different, it was concluded that the cholinergic neuroendocrine mechanisms regulating ovulation are related to the neural information arising from the ovaries and reaching the POA-AHA.
Journal of Endocrinology (1992) 133, 205–210
Effect of decapitation and chronic in-vivo treatment with a gonadotrophin-releasing hormone agonist on testicular steroidogenesis in the rat fetus
Authors: Habert R. 
Published: December 2008

ABSTRACT
To study the effect of in-vivo gonadotrophin-releasing hormone (GnRH) treatment on testicular testosterone production during late fetal life in the rat, 18·5-, or 20·5-day-old fetuses were decapitated and injected with either long-acting microcapsules containing the GnRH agonist d-Trp-6-GnRH or vehicle only. Two days later, fetal and maternal plasma was collected and fetal testes were removed and incubated for 6 h in medium with either 100 ng LH/ml or without LH. The GnRH agonist concentrations in the plasma of GnRH-treated decapitated male fetuses were comparable in the two age-related groups (5 nmol/l). After treatment of the fetus with d-Trp-6-GnRH, the agonist was recovered in maternal plasma, showing that this peptide can cross the fetal–maternal barrier. In 22·5-day-old decapitated vehicle-treated male fetuses, the plasma testosterone level dropped to that observed in control female fetuses, and treatment of decapitated male fetuses with the GnRH agonist did not further reduce it. At both days 20·5 and 22·5, basal in-vitro testosterone secretion by testes from decapitated vehicle-treated fetuses was lower than secretion by testes from intact control fetuses from the same litter, but LH-stimulated secretion was similar in both groups. Both basal and LH-stimulated secretion by testes from GnRH-treated decapitated fetuses was lower than secretion by testes from vehicle-treated decapitated fetuses and larger reductions were measured on day 22·5 than on day 20·5 (−48 vs −18% for basal secretion, and −76 vs −40% for LH-stimulated secretion).
These results suggest that, in contrast to immature Leydig cells, fetal Leydig cells are not desensitized to gonadotrophic stimulation after hypophysial deprivation, and that, in the rat, a negative testicular response to a putative intratesticular GnRH or to some other factor using the same intracellular pathway is established during late fetal life.
Journal of Endocrinology (1992) 133, 245–251
α-Melanocyte-stimulating hormone stimulates protein kinase C activity in murine B16 melanoma
Authors: Buffey J. , Thody A. J. , Bleehen S. S. , Neil S. Mac 
Published: December 2008

ABSTRACT
The effect of α-melanocyte-stimulating hormone (α-MSH) on protein kinase C activity and distribution was investigated in murine B16 F1 melanoma cells, α-MSH was found to induce an increased association of protein kinase C (PKC) activity with the particulate fraction of the cells, with an associated loss of enzyme activity from the soluble fraction. The peak response to α-MSH occurred between 20 and 60 min of incubation time, and enzyme activities redistributed to those seen in the control cells over the following 12 to 24 h. The average response to α-MSH (1 nmol/l) was an approximate 2·5-fold increase in the percentage of enzyme activity associated with the membrane within 1 h of exposure to α-MSH; the particulate enzyme activity represented 19·2 ± 4·4% of total activity in the absence of α-MSH and 50·7 ± 4·7% (means ± s.e.m., n = 9, P < 0·005) in the presence of α-MSH (1 nmol/l). Cells which had a relatively small percentage of their PKC activity on the membrane initially were significantly (P < 0·01) more responsive to α-MSH stimulation than cells which initially had a relatively large percentage of PKC activity on the membrane. The association of PKC activity with the membrane showed some evidence of being dose-related to α-MSH. This is the first report, to the best of our knowledge, of α-MSH activating PKC.
Journal of Endocrinology (1992) 133, 333–340
Immunoneutralization and immunocytochemical localization of inhibin α subunit during the mid-luteal phase in the stump-tailed macaque
Authors: Fraser H. M. , Smith K. B. , Lunn S. F. , Cowen G. M. , Morris K. , McNeilly A. S. 
Published: December 2008

ABSTRACT
The putative endocrine role of inhibin in the control of FSH secretion during the luteal phase in the primate was investigated by immunoneutralization. Antisera against the 1–23 amino acid sequence of the N-terminus of the human inhibin α subunit were raised in a ewe and three macaques. Antisera (10–20 ml) were administered to macaques on day 8/9 of the luteal phase and serum samples collected during the treatment cycle and post-treatment cycle for determination of FSH, oestradiol and progesterone. In addition, localization of inhibin within the macaque ovary at this stage of the luteal phase was investigated using the ovine antiserum. Intense immunostaining was localized within the granulosa-lutein cells of the corpus luteum with absence of staining in the thecalutein cells or other ovarian compartments. Administration of antisera was without significant effect on serum concentrations of FSH when compared with control animals, either during the first 24 h of detailed observation or for the following 10-day period of the late luteal phase and subsequent early follicular phase. These results provide further evidence that the corpus luteum is the major source of inhibin immunoreactivity during the primate menstrual cycle, but fail to support an endocrine role for inhibin in the suppression of FSH secretion.
Journal of Endocrinology (1992) 133, 341–347
The role of inhibin and oestradiol in the control of FSH secretion in the sheep
Authors: Mann G. E. , Campbell B. K. , McNeilly A. S. , Baird D. T. 
Published: December 2008

ABSTRACT
The relative importance of inhibin and oestradiol in the control of FSH and LH secretion in the ewe was investigated by passive immunization in intact animals and by hormone replacement therapy following acute ovariectomy, in the same experiment. Mature Scottish Blackface ewes on day 10 of the luteal phase were allocated to nine groups of four to five animals. Four groups were ovariectomized and immediately treated with either progesterone alone or in combination with steroid-stripped ovine follicular fluid ('inhibin') and/or oestradiol. Three further groups of ewes were left intact and injected with antibodies to the 1–26α peptide fragment of porcine inhibin and/or oestradiol-17β. Two groups of animals were either ovariectomized alone with no further treatment, or were left intact and treated with normal sheep plasma to act as controls. Blood samples were collected at 2 h intervals from 12 h before until 48 h after ovariectomy/immunization, and from 12 to 24 h after treatment, blood samples were collected at 10-min intervals.
After ovariectomy there was a large rise in the peripheral concentration of LH (P < 0·001) which was not affected by treatment with progesterone alone but was completely prevented by treatment with progesterone and oestradiol. Treatment with inhibin had no effect on this post-castrational rise in LH. In intact ewes, immunization against oestradiol, alone or in combination with inhibin, resulted in a rise in the concentration of LH, while immunization against inhibin had no effect on LH concentration. The peripheral concentration of FSH showed a significant (P < 0·001) increase after ovariectomy which was not affected by treatment with progesterone alone. Treatment with inhibin or oestradiol alone caused a significant (P < 0·01) reduction in this rise, while treatment with inhibin and oestradiol together completely prevented this post-castrational rise in FSH concentration. Passive immunization against inhibin or oestradiol alone resulted in a transitory (P< 0·01) rise in the peripheral concentration of FSH, while immunization against the two hormones in combination resulted in a significantly (P < 0·01) larger rise. During the 14-h period after treatment, the rise in the concentration of FSH in this combined immunization group was not significantly different from that seen in the control ovariectomized group.
These results provide evidence that FSH secretion is under the control of both oestradiol and inhibin, while reinforcing the hypothesis that inhibin is not involved in the regulation of LH production, which is under the dual control of oestradiol and progesterone.
Journal of Endocrinology (1992) 133, 381–391
What is a normal stimulated growth hormone concentration?
Authors: Dattani M. T. , Pringle P. J. , Hindmarsh P. C. , Brook C. G. D. 
Published: December 2008

ABSTRACT
In a retrospective analysis, we have compared the response of serum GH concentration to insulin-induced hypoglycaemia in 148 short prepubertal children (114 males, 34 females) aged between 3·9 and 11·9 years with the growth rate of the individual to determine 'cut-off' values for the diagnosis of GH insufficiency.
Sixty-three children grew with a height velocity standard deviation score (SDS) greater than −0·8 (group 1), which represents the growth velocity of children progressing along or closely parallel to the third height centile. Eighty-five children had a height velocity SDS of less than −0·8 (group 2). Median peak serum GH concentration responses to insulin-induced hypoglycaemia were 19·9 mU/l (range 1·5–54·4) in group 1 and 9·9 mU/l (range 0·7–46·2) in group 2 (Mann–Whitney; P < 0·001).
Using growth rate as the determinant of normality, the efficiency, sensitivity and specificity of the insulin-induced hypoglycaemia test were calculated using different serum GH concentration cut-off values to diagnose GH insufficiency. In our (Hybritech) assay, a cut-off value of 13·5 mU/l provided optimal performance in terms of efficiency (66%), sensitivity (64%) and specificity (70%).
The response of serum GH concentration to insulin-induced hypoglycaemia in short children growing at different growth rates was continuous. Each laboratory measuring serum GH concentrations needs to construct its own 'normal' cut-off value.
Journal of Endocrinology (1992) 133, 447–450