bluuebunny/crossref_metadata_2025_split huggingface dataset:
A 5‐Day Estradiol Therapy, in Amounts Reproducing Concentrations of the Early‐Mid Follicular Phase, Prevents the Activation of the Hypothalamo‐Pituitary‐Adrenal Axis by Interleukin‐1α in the Ovariectomized Rhesus Monkey
Authors: Xia‐Zhang Linna , Xiao Ennian , Ferin Michel 
Published: September 2006

AbstractIn a previous report, we have shown that intracerebroventricular (icv) administration of the cytokine interleukin‐1a (IL‐1α) in the ovariectomized (OVX) rhesus monkey results in the acute activation of the hypothalamo‐pituitary‐adrenal (HPA) axis and the inhibition of LH and FSH secretion. Here, we compare the cortisol response to IL‐1α administration in OVX monkeys and in OVX animals replaced with estradiol (E) to reproduce E concentrations typical of the early‐mid follicular phase. Cortisol, LH and FSH were measured after an icv infusion of physiological saline or IL‐1α (2.1 or 4.2 μg/30 min) in both groups. E‐containing capsules were implanted sc 5 days prior to the experiment. In OVX, E concentrations were <5 pg/ml. Cortisol concentrations decreased throughout the afternoon after saline infusion (to 49.7 ± 5.1% of baseline at 5 h; n = 7), but increased significantly after IL‐1α to 158.3 ± 13.8% (n = 7). In OVXE, cortisol also declined after saline (to 76.4 ± 16.2%; n = 5). There were 2 types of response to IL‐1α: in grp 1 (mean E 18.0 ± 0.7 pg/ml), the cortisol response was similar to that in OVX (160.8 ± 17.0%; n = 5), while in grp 2 (E: 30.7 ± 3.1 pg/ml), the cortisol response was absent (66.6 ± 7.2% of baseline at 5 h; NS vs saline in OVXE; n = 7). The cortisol response to IL‐1α was restored in 2 monkeys when E was increased to >100 pg/ml, confirming our previous observations. While saline infusion did not affect LH (102.3 ± 10.2% of baseline at 5 h) or FSH (102.5 ± 4.4%) secretion in OVX monkeys, there was a significant decrease in both hormones after IL‐1α (LH: 33.3±3.7%, FSH: 66.2 ± 6.5%; P<0.05 vs saline). This effect was lessened in OVXE animals: By 5 h, areas under the LH curve were 62.8 ± 10.9% of baseline in grp 1 and 85.3 ± 7.9% in grp 2 (NS vs saline), while those under the FSH curve were 84.0 ± 6.5% in grp 1 and 77.7 ± 4.3% in grp 2 (NS vs saline).The data demonstrate a striking effect of a 5‐day estradiol treatment in preventing the HPA axis response to the cytokine IL‐1α in the OVX monkey. This action, however, occurs only within restricted estradiol concentrations that reproduce E levels typical of the early‐mid follicular phase of the menstrual cycle. While the precise mechanism through which estradiol exerts this action remains to be investigated, the results may have clinical relevance to the issue of estrogen replacement therapy in physiology and pathology.
Induction of Cellular Follicle‐Stimulating Hormone in the Hamster Adenohypophysis Requires Intermittent Stimulation by Luteinizing Hormone Releasing Hormone
Authors: Woller Michael J. , Campbell Gary T. , Blake Charles A. 
Published: September 2006

AbstractWe investigated the effectiveness of continuous vs intermittent LHRH stimulation of the neonatal female anterior pituitary gland on inducing cellular FSH immunoreactivity in the Golden Syrian hamster. Neonatal female pituitary glands were grafted beneath the right renal capsules of hypophysectomized‐ovariectomized adult hosts with a catheter implanted in the external jugular vein. In experiment 1, vehicle or LHRH (6 ng/h) was infused continuously or LHRH was pulsed at 1 h (6 ng) or 12 h (72 ng) intervals through the catheters for 8 days. Hamsters were decapitated for collection of trunk blood shortly after the end of treatment, and grafts were prepared for immunocytochemical staining for LH and FSH. Anterior pituitary glands removed from neonatal (day 1) and day 9 female pups also were stained for LH and FSH. The mean percentage of adenohypophysial cells staining for LH increased from 11% in neonatal pups to mean percentages (24‐28%) that were similar in day 9 pups and in all groups with grafts. The mean percentage of adenohypophysial cells staining for FSH increased from 1% in neonatal pups to percentages (16–21%) that were similar in day 9 pups and in grafts in hosts administered 6 or 72 ng LHRH pulses. By contrast, the mean percentage of FSH cells did not increase in grafts in hosts administered vehicle or LHRH by continuous infusion. Serum LH concentration was low in hosts given vehicle or LHRH by continuous infusion but elevated in hosts given 72 ng LHRH pulses and in all but one host given 6 ng LHRH pulses. Serum FSH concentration was detectable in some of the hosts given 6 or 72 ng LHRH pulses and non‐detectable in the rest of the hosts. In experiment 2, the mean percentage of adenohypophysial cells staining for FSH did not increase in grafts in hosts infused with LHRH continuously at 72 ng/h compared to that observed in hosts pulsed with vehicle every h for 8 days (1.4 vs 2.0%). The data demonstrate that intermittent but not continuous stimulation of neonatal female adenohypophysial cells by LHRH is effective in inducing cellular FSH immunoreactivity. The data also strongly suggest that LHRH release is episodic during the first week after birth in the female hamster. To our knowledge, these results are the first to provide evidence suggesting that the episodic LHRH release system is functioning to exert an important biological effect in a neonatal mammal and that the mechanism for down‐regulation of LHRH receptors in gonadotrophs can be activated this early in life.
Regulation of Corticotropin‐Releasing Factor Secretion and Synthesis in the Human Neuroblastoma Clones‐ BE(2)‐M17 and BE(2)‐C
Authors: Kasckow John W. , Han Jin‐Hee , Parkes David G. , Mulchahey Jeffrey J. , Owens Michael J. , Risby Emile D. , Fisher Jennifer , Nemeroff Charles B. 
Published: September 2006

AbstractThe BE(2)‐M17 and BE(2)‐C human neuroblastoma cell lines have been shown to synthesize and secrete corticotropin‐releasing factor (CRF) following retinoic acid treatment. It has been demonstrated that CRF secretion and intracellular synthesis increases in response to forskolin treatment. In this report, we have further characterized these cells in response to protein kinase C activators, dexamethasone, interleukin—1x, as well as various neurotransmitters and peptides. Nanomolar concentrations of the phorbol ester—phorbol 12 myristate 13—acetate (TPA), increased intracellular CRF content in both cell lines while increasing secretion only in the BE(2)‐M17 cell. Nanomolar concentrations of dexamethasone were not able to alter basal levels of secretion and content in either cell type. However, in the BE(2)‐Ml7 cell but not the BE(2)‐C cell, the same concentrations of dexamethasone added to 30 μM forskolin augmented levels of CRF secretion and content. Likewise, the same augmented response in CRF secretion and content was seen only in the BE(2)‐M17 cell line when nanomolar concentrations of dexamethasone were added to 20 nM TPA. Furthermore, only in the BE(2)‐M17 cell line were micromolar levels of the biogenic amine serotonin able to increase levels of CRF secretion and content. No effects on CRF in both cell lines were demonstrable with picomolar levels of interleukin‐10: as well as micromolar levels of acetylcholine, norepinephrine, arginine‐vasopressin, oxytocin, and angiotensin‐II. The potential usefulness of these cells as models of central nervous system or placental CRF‐containing neurons is discussed.
S–100 Antigen‐Positive Folliculostellate Cells are not the Source of IL‐6 Gene Expression in Human Pituitary Adenomas
Authors: Ueta Yoichi , Levy Andrew , Chowdrey Hardial S. , Lightman Stafford L. 
Published: September 2006

AbstractWe have investigated the expression of IL‐6 in a random selection of 27 human pituitary adenomas, comprising 8 somatotroph, 5 corticotroph, 3 mammotroph and 11 endocrinologically inactive adenomas, using a 35S‐labelled 1.1kb riboprobe complementary to human IL‐6. Positive and negative IL‐6 transcript controls were generated from the IL‐6‐secreting human bladder carcinoma cell line T24/83. Tissue from a malignant melanoma was used as a positive S‐100 immunocytochemical control tissue. Of the 27 human pituitary adenomas examined by in situ hybridization, 7 (26%) contained IL‐6 transcripts: these were 3 of 5 corticotroph adenomas, 2 of 8 somatotrophinomas and 2 of 11 endocrinologically inactive adenomas. In each case, IL‐6 transcript‐positive cells constituted less than 1% of the total pituitary tissue mass examined. Alternate wax embedded 3 μm thick sections from 5 of the 7 IL‐6 transcript positive tumours were examined immunocytochemically for S‐100 antigen, or by in situ hybridization for IL‐6 transcripts. Immunocytochemistry for S‐100 antigen was completely negative in 3 of the 5 tumours and in the remaining 2, there was no evidence of IL‐6 transcripts and S–100 antigen co‐localization in any of the sections examined. This suggests that in pituitary adenomas, cells other than classical folliculostellate cells are responsible for IL‐6 production.
Sexually Dimorphic Expression of Androgen Receptor Immunoreactivity by Somatostatin Neurones in Rat Hypothalamic Periventricular Nucleus and Bed Nucleus of the Stria Terminalis
Authors: Herbison Allan E. 
Published: September 2006

AbstractGonadal steroids exert important regulatory actions on the hypothalamic neurones regulating growth hormone secretion and are believed to play a role in generating its sexually dimorphic pattern of secretion. Recent evidence indicates that estrogen actions on one of these neural populations, the periventricular somatostatin (SOM) neurones, are likely to be indirect as they do not possess nuclear estrogen receptors in either sex although androgen receptors (ARs) have been reported within these cells in male rats. The present study has used double‐labelling immunocytochemistry procedures to examine whether sex differences exist in AR expression by SOM neurones located in the periventricular nucleus and bed nucleus of the stria terminalis (BNST). Within the hypothalamus, SOM‐immunoreactive neurones were found concentrated in the periventricular nucleus while both anterior and posterior divisions of the BNST contained scattered populations of SOM cells. Cells immunoreactive for the AR were detected in all of these areas. Although the intensity of AR cell nuclei staining was equivalent in males and females in regions such as the lateral septum, the intensity of AR staining in many individual cells of the periventricular nucleus and posterior BNST of the female was reduced when compared with the male. Double‐labelling experiments revealed that approximately 40% of periventricular SOM neurones expressed AR immunoreactivity in the male compared with significantly (P<0.01) fewer cells in the female (∼7%). In the BNST, double‐labelled cells were only detected within the principle encapsulated, interfascicular and transverse nuclei of its posterior division. Approximately 60% of SOM cells in these nuclei expressed AR immunoreactivity in the male while significantly (P<0.01) fewer did so in the female (∼25%). These results indicate that substantial sex differences exist in AR expression by SOM neurones in both the periventricular nucleus and BNST. Such differences in AR expression by periventricular SOM cells may contribute to their sexually dimorphic nature and, consequently, sex differences in growth hormone secretion.
Species Differences in Estrogen Receptor and Progesterone Receptor‐mRNA Expression in the Brain of Sexual and Unisexual Whiptail Lizards
Authors: Young Larry J. , Nag Pratip K. , Crews David 
Published: September 2006

AbstractCirculating concentrations of gonadal steroid hormones and reproductive behavior in female vertebrates vary as a function of ovarian state. Steroids secreted by the ovary, specifically estrogen and progesterone, influence the expression of behaviors associated with reproduction by interacting with intracellular sex steroid receptors located in specific regions of the brain. Using in situ hybridization, we analyzed estrogen receptor and progesterone receptor messenger RNA expression in several brain regions of ovariectomized, vitellogenlc, and postovulatory individuals from two species of whiptail lizards (Cnemidophorus uniparens and C. inornatus). Although these species are genetically very similar, they differ in two aspects of their reproductive biology: (i) the unisexual C. uniparens alternate between expressing female‐typical and male‐like pseudosexual behaviors while female C. inornatus normally express only female receptive behavior, and (ii) circulating estradiol concentrations in reproductively active female C. uniparens are approximately five‐fold lower than in reproductively active female C. inornatus. We found that the regulation of sex steroid receptor gene expression was region specific, with receptor‐mRNA expression being increased, unchanged, or decreased during vitellogenesis depending on the area. Furthermore, Several species differences in the amount of sex steroid receptor‐mRNA were found that may be relevant to the species differences in circulating estrogen concentrations and sexual behavior.
Glial Ensheathment of GnRH Neurons in Pubertal Female Rhesus Macaques
Authors: Witkin Joan W. , O'Sullivan Honor , Ferin Michel 
Published: September 2006

AbstractDuring the period of development, prior to full sexual maturity, gonadotropin hormone‐releasing hormone (GnRH) neurons are fully capable of synthesizing and processing the GnRH decapeptide. Nonetheless, the secretion of the hormone is not adequate to stimulate adult patterns of gonadotropin release. The present study was undertaken to examine ultrastructural characteristics of the GnRH neuron and its relationship to its environment in early‐ midpubertal female rhesus monkey. These neurons bore all the ultrastructural immunocytochemical characteristics of those in mature animals, but quantitative morphometrics revealed that they were extensively apposed by glial processes. Such ensheathment was described earlier in ovariectomized adult animals and was found to be reversible by administration of gonadal steroids. The density of synaptic input to GnRH neurons in the pubertal animals did not differ significantly from that of adult intact or ovariectomized animals from a previous study. Chemical identification will be required to determine whether there are age or hormonal differences in the innervation of these neurons.These results provide anatomical evidence in support of indications from other studies that the ovarian steroidal milieu affects GnRH‐glial relationships. Further testing will be required to determine whether the attainment of sexual maturity in the female rhesus macaque is dependent upon a reduction in glial ensheathment of GnRH neurons.
A Technique for Sorting Rat Gonadotropes using Anti‐LH or Anti‐FSH Antibodies Covalently attached to Magnetic Beads
Authors: Valenti S. , Sarkissian A. , Giusti M. , Giordano G. , Dahl K. D. 
Published: September 2006

AbstractA technique for sorting live LH‐ and FSH‐secreting cells was developed. After enzymatic dispersion, a suspension of pituitary cells from male rats castrated 7 days earlier was incubated in potassium chloride (KCI 50 mmol/l) for 30 min and gonadotropin outflow was provoked. Then, considering either LH or FSH as temporary surface markers, we positively selected the secreting cells by means of antibodies toward either LH (anti‐LH beads) or FSH (anti‐FSH beads) covalently attached to magnetic beads. The spontaneous secretion of LH and FSH overnight and the release induced by KCI the following morning were calculated. A population enriched in gonadotropes (16% of the total) able to secrete both gonadotropins was selected by means of anti‐LH beads; this released 7 times as much LH as non‐selected cells. A similar population (14% of the total) was selected by means of anti‐FSH‐coated beads; this produced 3.3 times as much LH as non‐selected cells.In some experiments, the cells not previously sorted with anti‐LH‐coated beads were further incubated in the presence of anti‐FSH beads, in an attempt to isolate a population secreting only FSH. A limited number of cells were sorted (6% of the total cells), able to produce both gonadotropins, but with a lower LH/FSH ratio.Similarly, those cells excluded by the selection with anti‐FSH beads were further incubated with anti‐LH beads, with a view to obtaining only‐LH‐secreting cells. However, both gonadotropins were still secreted by these cells (8% of the total), which had the highest LH/FSH ratio.In conclusion, fractions from castrated male rats that are enriched in gonadotropes contain cells that secrete both gonadotropins in vitro. The secretion of LH is prevalent. However, differences in the LH/FSH ratio between the populations sorted and changes from spontaneous to stimulated release are observed. This suggests that some gonadotropes might ‘specialize’ in releasing LH and others in releasing both LH and FSH.
Effect of Parathyroid Hormone and Calcitonin on Cholinergic Markers in Rat Parathyroid Gland
Authors: Stern Javier E. , Cardinali Daniel P. 
Published: September 2006

AbstractThe effect of parathyroid hormone (PTH) and calcitonin on 3H‐choline uptake and on 3H‐acetylcholine synthesis by rat parathyroid glands were examined. Incubation of tissue for 120 min with PTH or calcitonin resulted in an inverted bell‐shaped, dose‐dependent inhibition of 3H‐choline uptake, with a maximal effect at 10−9 M Concentration. The effect of PTH on parathyroid choline uptake was blunted by preincubation with the PTH antagonist NLe8–18 ‐PTH (3–34) amide. PTH brought about a dose‐dependent inhibition of 3H‐choline conversion to 3H‐acetylcholine, with significant effects at 10−8 M concentration or higher. This inhibitory effect of PTH on 3H‐acetylcholine synthesis was blocked by co‐incubation with the PTH antagonist NLe8–18‐PTH (3–34) amide. Only at a 10−7 M concentration calcitonin was effective to impair the in vitro conversion of radioactive choline into 3H‐acetylcholine by parathyroid fragments. The results indicate that, in vitro, PTH, and to a less extent, calcitonin, inhibit cholinergic activity in rat parathyroid glands.
Mechanism of Action of Pituitary Adenylate Cyclase‐Activating Polypeptide (PACAP) in Human Nonfunctioning Pituitary Tumors
Authors: Lania Andrea , Gil‐del‐Alamo Paloma , Saccomanno Katia , Persani Luca , Faglia Giovanni , Spada Anna 
Published: September 2006

AbstractSeveral evidence suggest that pituitary adenylate cyclase activating polypeptides (PACAP‐38 and ‐27) could function as hypophysiotropic factors. Both peptides interact with either the type I receptor, which preferentially binds the two PACAPs and has a much lower affinity for vasoactive intestinal polypeptide (VIP) or the type II receptor, which binds the two PACAPs and VIP with a nearly equal affinity. In addition to the stimulation of adenylyl cyclase (AC) activity, in different cell types PACAP causes an increase of cytosolic calcium levels ([Ca2+]i), consequent to phospholipase‐C activation. In the present study, we investigated the effect of PACAP on cAMP formation and [Ca2+]i levels in 16 human nonfunctioning pituitary adenomas (NFPA). PACAP‐38 increased cAMP formation in all tumors; the peptide stimulated either AC activity in membrane preparations from 26 ± 10 to 214 ± 179 pmol/mg prot/min (P < 0.01) or cAMP efflux from 12 ± 5.4 to 73.2 ± 32 pmol/well (P < 0.01) in cultured cells. The effect, detectable at concentrations higher than 1‐10 pM, was maximal at 0.1‐10 nM. While PACAP‐38 and PACAP‐27 were nearly equally effective and potent, 100‐fold higher concentrations of VIP were required to obtain similar AC activation. GHRH and CRH were ineffective in any NFPA. The PACAP effect was not antagonized by a VIP antagonist, while PACAP fragment 6–27 amide partially reduced the stimulatory effects of both PACAP‐27 and VIP in 2 out of 3 tumors tested. PACAP‐38 caused a [Ca2+]i rise in cells obtained from 7 NFPA (from 110 ± 34 to 151 ± 40 nM [Ca2+]i, P < 0.05) while in the remaining 7 the peptide was ineffective at any concentrations tested (from 1 nM to 10 μM). In the responsive tumors, PACAP‐38 effect was not consequence of phospholipase‐C activation since removal of extracellular Ca2+ as well as blockade of L‐type Ca2+ channels by dihydropyridine antagonists abolished [Ca2+]i increase triggered by the peptide. These data indicate that PACAP is by far the most potent activator of cAMP formation in NFPA and suggest a possible modulatory action of this peptide on cell growth.
Effects of Continuous and Repetitive Administration of a Potent Analog of GH‐RH(1–30)‐NH2 on the GH Release in Rats Treated with Monosodium Glutamate
Authors: Kovács Magdolna , Fáncsik András , Hrabovsky Erik , Mezö Imre , Teplán István , Flerkó Béla 
Published: September 2006

AbstractTo assess the efficacy of a potent GH‐releasing hormone (GH‐RH) analog (D‐Ala2, Nle27, Gaba30‐GH‐RH‐(1–30)‐amide) in the treatment of GH deficiency, we investigated the effects of chronic administration of this analog (A‐495) on growth responses in monosodium glutamate (MSG)‐lesioned rats. Basal serum GH concentrations, GH responses to bolus injections of GH‐RH, as well as acceleration of body gain and linear growth were compared after long‐term continuous and repetitive administration of A‐495. The effects of continuous and repetitive administration of the analog on GH responses in vitro were also compared using the superfused pituitary cell system method. Treatment with MSG reduced the body weight and linear growth of the animals (− 22% and −11%, respectively), the basal serum GH concentration (− 66%), and the GH‐RH‐induced absolute GH responses (− 61%) but did not alter the relative GH responses (to basal GH concentrations). Repetitive administration of 10 pg daily doses of A‐495 at 24 h intervals for 2 weeks highly increased the GH responsiveness to GH‐RH and induced catch‐up growth, by which MSG‐treated animals achieved the growth rate of normal controls. However, basal serum GH concentrations were only modestly enhanced. Continuous infusion of A‐495 at the same daily dose resulted in slight increases in the GH‐RH‐induced GH rises, moderate acceleration of body gain, and no change in linear growth. Basal serum GH concentrations were not significantly influenced by this treatment. These results demonstrate that exogenous GH‐RH pulses administered at lower frequency than the frequency of the physiological GH secretion are able to fully restore the normal growth rate of the GH deficient rats. The effectivity of the treatment is rather dependent on the magnitude of GH rises than the basal GH level. Although continuous administrations of the GH‐RH is also have some effect on the body gain, repetitive administration is more effective at the same daily dose. Our results from in vitro experiments show that, in addition to the low magnitude of the GH‐RH‐stimulated GH rises, desensitization of the GH secretory response might also be accounted for the low effectivity of the continuously administered GH‐RH. Present results demonstrate the therapeutic usefulness of our new GH‐RH analog and are the first to evidence that GH‐RH need not be administered as frequently as the appearance of the endogenous GH pulses to restore the normal growth of the GH deficient rats.