bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antiovulatory Doses of Antagonists of LH‐RH Inhibit LH and Progesterone but not FSH and Estradiol Release
Authors: Kovács Magdolna , Koppán Miklós , Mezö Imre , Teplán István , Flerkó Béla 
Published: September 2006

AbstractThe differential regulation of immunoactive FSH and LH secretion by endogenous LH‐RH was studied using LH‐RH antagonists (Ac‐D‐Trp1,2, D‐Cpa2, D‐Lys6, D‐Ala10LH‐RH (MI‐1544) and (Ac‐D‐Nal1, D‐Phe(pCI2), D‐Trp3, D‐Cit6, D‐Ala10LH‐RH (SB‐030) in ovariecto‐mized (OVX) and regularly cycling rats. Single injections of 10 μg and 100 μg doses and long‐term treatment with 10 μg doses of MI‐1544 were used in OVX animals. Serum and pituitary LH and FSH, as well as serum estradiol and progesterone was determined by RIA during and/or after the treatment. Single injections of MI‐1544 in OVX animals caused prompt (in 2 h) and long‐lasting (for more than 24 h) suppression of the serum LH, while no or late decrease (after more than 6 h) of the serum FSH. Long‐term treatment with the same analog decreased the serum LH (by 50%) and moderately increased the pituitary LH (by 21%) but did not change the serum and the pituitary FSH concentrations. In normal rats, long‐term treatment with both of our analogs also resulted in divergent alterations in the LH and FSH concentrations. Serum LH dropped to undetectable levels, while serum FSH did not change significantly. Pituitary LH increased (by 31 to 41%), while FSH decreased (by 27 to 38%). Marked depression was found in the serum progesterone (by 64%) but no significant change in the serum estradiol levels, after the long‐term treatment for 21 days. The ovarian cycles were interrupted, and no ovulation appeared during the treatment. Significant decrease was detectable in the weight of the ovaries (by 46%), whereas the weight of the uteri did not change or slightly elevated (by 22%), after the treatment with SB‐030 or MI‐1544, respectively. The clear antagonistic effect of the analogs on the LH‐RH‐stimulated LH and FSH release was tested in the in vitro superfused rat pituitary cell system. In this system our analogs provented both the LH‐and the FSH‐releasing effect of the LH‐RH. The inhibitory effect was longer‐lasting on the FSH than on the LH release. Our studies give evidences that the long‐term treatment with antiovulatory doses of LH‐RH antagonists suppress the LH and progesterone but not the FSH and estradiol secretion and indirectly support the earlier publications suggesting the presence of FSH‐releasing factor(s) in the CNS.
Gonadal Steroids have Paradoxical Effects on Brain Oxytocin Receptors
Authors: Insel Thomas R. , Young Larry , Witt Diane M. , Crews David 
Published: September 2006

AbstractSpecific brain receptors for oxytocin have been described in several mammalian species. The distribution of these receptors differs greatly across species and in the rat, receptor binding in specific brain regions appears to depend upon gonadal steroids. This study used in vitro receptor autoradiography to examine the effects of testosterone on oxytocin receptor binding in the mouse forebrain. Three groups of male mice were compared: castrates treated with blank capsules, castrates treated with testosterone filled capsules, and intact males. Irrespective of steroid treatment, the distribution of oxytocin receptors in mouse forebrain differed markedly from patterns previously described in the rat. In addition to these species differences in receptor distribution, testosterone had effects in the mouse which differed from the induction of receptors previously reported in the rat. In the mouse ventromedial nucleus of the hypothalamus, binding in the untreated castrate males was approximately double that observed in either the intact or the testosterone‐treated castrates. In other regions of the mouse brain, such as the intermediate zone of the lateral septum, binding to oxytocin receptors was increased with testosterone treatment. These results suggest that the brain oxytocin receptor varies across species not only in its distribution but also in its regional regulation by gonadal steroids. These apparently paradoxical changes in oxytocin receptor binding may result from either direct or indirect effects of gonadal steroids in mouse brain.
Differential Effects of Estrogen and Progesterone on Levels of POMC mRNA Levels in the Arcuate Nucleus: Relationship to the Timing of LH Surge Release
Authors: Petersen S. L. , Keller M. L. , Carder S. A. , McCrone S. 
Published: September 2006

AbstractBeta‐endorphin is thought be an important inhibitor of LHRH neuronal activity and also to play a role in conveying information about changes in steroid levels to LHRH neurons. We have previously shown that the mRNA encoding the precursor of ß‐endorphin, proopiomelanocortin (POMC), fluctuates during the estrous cycle with the most dramatic changes occurring on proestrus. POMC mRNA levels decline before the onset of LH surge release but then dramatically rise and remain elevated during the surge. In the present studies we tested the hypothesis that the decline in POMC mRNA levels immediately before the proestrous LH surge is mediated by estrogen and the rise during the surge by progesterone. To test this hypothesis, we compared changes in POMC mRNA levels between ovariectomized (OVX) and OVX estrogen (E2)‐treated rats and between OVX E2‐treated rats with and without progesterone. Animals were examined at hourly intervals after the administration of progesterone, then at every 4h during the LH surge. Using in situ hybridization histochemistry, we found that E2 decreased POMC mRNA levels in OVX rats before the onset of the LH surge and further suppressed levels during the surge. Compared to animals treated with E2 alone, progesterone advanced the time at which both the LH surge began and the time at which POMC mRNA levels declined. After a transient decline, POMC mRNA levels rose in these progesterone‐treated animals and remained elevated throughout the period of the LH surge. These results support the hypothesis that progesterone times the LH surge and limits its appearance to one day by exerting a biphasic effect on the activity of ß‐endorphinergic neurons of the arcuate nucleus.
Autonomie Control of Penile Erection: Modulation by Testosterone in the Rat
Authors: Giuliano François , Rampint Olivier , Schirar Alain , Jardin Alain , Rousseau Jean‐Paul 
Published: September 2006

AbstractThe role of testosterone on peripheral autonomie control of penile erection was studied in rats. Erectile response to cavernous nerve stimulation was measured by intracavernous pressure associated with arterial blood pressure monitoring in anesthetized adult males. Comparison was performed between control (Co), castrated (Ox) and castrated, testosterone‐replaced (OxT) rats. Ox rats exhibited smaller erectile responses. Testosterone replacement restored these responses in OxT rats. To identify the peripheral target of testosterone, postganglionic neurons of the major pelvic ganglion, innervating the corpora cavernosa through the cavernous nerves, were separated from the spinal cord by preganglionic axotomy of the pelvic nerves in three other groups of rats (PNx). Erectile response was unchanged in PNx rats, decreased in OxPNx more than in Ox rats, and restored by testosterone replacement (OxPNxT rats). We ruled out the participation of a somatic component in the erectile response in this model as there was no difference between curarized and Co rats. We infer that testosterone enhances the erectile response of cavernous nerve stimulation, acting peripherally to the spinal cord. Arguments are provided that the sites of action for testosterone or its metabolites are situated on neurons rather than on penile erectile tissue. Proerectile postganglionic parasympathetic neurons seem to be the exact target for gonadal steroids.
Expression of Growth Hormone Receptor Gene in Rat Hypothalamus
Authors: Minami Shiro , Kamegai Jun , Hasegawa Osamu , Sugihara Hitoshi , Okada Kenmei , Wakabayashi Ichiji 
Published: September 2006

AbstractGrowth hormone receptor (GHR) mRNA‐expressing cells in the hypothalamus were observed using hybridization histochemistry in adult male rats. Digoxigenin‐labeled cRNA corresponding to the extracellular part of rat GHR was used as a probe. Northern blotting analysis of hypothalamic total RNA from adult male rats revealed that the 4.5 kilobase (kb) transcript of the GHR gene corresponding to the GHR messenger RNA (mRNA) predominated over the 1.2 kb transcript corresponding to GH‐binding protein mRNA. GHR mRNA‐containing cells were observed in the arcuate nucleus (ARC), the periventricular nucleus (PeV), ventrolateral region of the ventromedial nucleus, the paraventricular nucleus and the supraoptic nucleus. To further understand the significance of the GHR gene expression in the hypothalamus, the effect of in vivo manipulation of GH on the somatostatin (SS) gene expression in the ARC and PeV, and the GRF gene expression in the ARC was observed among adult male rats using in situ hybridization histochemistry. Ten days after hypophysectomy, the SS mRNA level in the ARC as well as PeV was significantly lower than that in the respective nuclei of sham‐operated control rats, while the GRF mRNA level in the ARC was significantly higher than that in the ARC of control animals. Subcutaneous injection of recombinant human GH (0.33 mg) to hypophysectomized rats every 12 h for 5 days restored the SS mRNA level in the ARC and PeV, and reduced the GRF mRNA level in the ARC to that of control animals. The data suggest that GH directly acts on the hypothalamic PeV and ARC, and alters the gene expression of SS and GRF.
Re‐Evaluation of Gonadotropin‐Releasing Hormone (GnRH) Action on Pituitary Cell Differentiation with Special Regard to its Effect on LH and TSH Cell Types
Authors: Héritier Anne G. , Dubois Paul M. 
Published: September 2006

AbstractWe have previously demonstrated that TRH induces several hypophyseal cell type differentiation. In the present study, we re‐evaluated the effect of GnRH on gonadotroph differentiation, and we determined whether gonadotropin is implicated in the appearance of other pituitary cell types. These effects were compared to the influence of TRH on LH and TSH cell differentiation. Pituitary primordia of 11 day‐old rat embryos were cultured in a synthetic medium until the equivalent of term, and the LH and TSH cell differentiation was visualized using an immunohistochemical technique. The effect of GnRH on pituitary hormone cells was evaluated by measuring the percentage of immunoreactive area per section.GnRH, when added on the first day of culture, induced LH and TSH cell differentiation in a dose‐dependent manner. GnRH was more effective than TRH in inducting gonadotropic phenotype expression. This suggests that GnRH, which evokes LH release, is the most effective factor inducing gonadotroph differentiation in early fetal life. However, GnRH was as effective as TRH in thyrotroph differentiation. Lactotrophs were detected in primordia cultured with GnRH. As lactotroph phenotype differentiation is controlled by the a‐subunit of glycoproteic hormone, further studies are required to determine whether or not GnRH effect on lactotroph is direct. GnRH did not affect the corticotroph and somatotroph differentiation. These results confirm that hypothalamic factors such as TRH or GnRH are capable of inducing more than one pituitary cell phenotypes.
Colocalization of Natriuretic Peptide and Estrogen Receptor Immunoreactivities in Preoptic Nuclei in the Female Rat
Authors: Watson Robert E. , Hutchinson Robert K. , Langub M. Chris , Landis John W. , Seksaria Shikha , Rainey David M. , Keil Lanny C. 
Published: September 2006

AbstractEstrogen is known to play an important role in regulating reproductive function in female rats through actions exerted at the preoptic area, a part of the brain that is markedly sexually dimorphic and which contains abundant estrogen receptors. A critical question to our understanding of estrogen's action on the brain is to identify the types of neurons that contain estrogen receptors (ER). Previous studies have shown that atrial natriuretic peptide (ANP) is in abundance in the preoptic area, and that ANP and other natriuretic peptides are capable of regulating gonadotropin secretion. In an effort to determine whether ERs are present in natriuretic peptide‐immunoreactive (NP‐ir) neurons in the preoptic area of the rat, double label immunocytochemistry was performed. Since ER‐ir, as demonstrated with antibody H222 is known to be localized predominantly in cell nuclei, while NP‐ir is present in the cytoplasm, single cells can be double labeled. Diaminobenzidine tetrahydrochloride was used for localization of NP‐ir neurons, while nickel‐enhanced diaminobenzidine tetrahydrochloride was used for localization of ER‐ir. The results revealed that many nuclei throughout the preoptic area contained neurons that were ER‐ir or NP‐ir and that a substantial number were double labeled. Cell counts in selected preoptic nuclei and components, including the anteroventral periventricular nucleus, periventricular preoptic nucleus, medial part of the medial preoptic nucleus, and central part of the medial preoptic nucleus revealed that 13.6%, 11.1%, 13.5%, and 24.4%, respectively, of the NP‐ir neurons in these nuclei also contained ER‐ir. Collectively, a total of 14.9% of the NP‐ir neurons in these nuclei also contained ER‐ir. These results support the hypothesis that estrogen may regulate the activity of NP‐ir cells in the preoptic area and thereby may be capable of altering functions associated with NPs in this region of the brain, including not only regulation of gonadotropin secretion, but also control of blood pressure and fluid balance.
Projections from Ventrolateral Hypothalamic Neurons Containing Progestin Receptor‐ and Substance P‐Immunoreactivity to Specific Forebrain and Midbrain Areas in Female Guinea Pigs
Authors: Ricciardi Kirsten H. Nielsen , Blaustein Jeffrey D. 
Published: September 2006

AbstractMany neurons within the ventrolateral hypothalamus in guinea pigs contain estrogen‐induced progestin receptors as well as substance P. Retrograde tracing combined with immunocytochemistry was used to determine the specific projections of this subset of steroid‐ sensitive cells. Unilateral Fluoro‐Gold injections into the dorsal midbrain, including the central gray, labeled a large proportion of the ventrolateral hypothalamic neurons immunoreactive for both progestin receptors and substance P (approximately 30%); substantially fewer of these neurons were labeled by unilateral Fluoro‐Gold injections into the preoptic area (approximately 6%), medial amygdala (approximately 10%), or the bed nucleus of the stria terminalis (approximately 11 %). The projections of progestin receptor‐immunoreactive neurons in the ventrolateral hypothalamus were similar to those of progestin receptor/substance P double‐labeled neurons, while a slightly lower percentage of the ventrolateral hypothalamic, substance P‐immunoreactive neurons tended to project to each of these areas. These pathways may prove to be components of the neural circuitry underlying a variety of functions influenced by gonadal steroid hormones and substance P, such as female sexual behavior, salt intake, nociception and aggression.
Interleukin‐1β and lnterleukin‐6 Stimulate Neurohypophysial Hormone Release in vitro
Authors: Yasin Sharifah A. , Costa Alfredo , Forsling Mary L. , Grossman Ashley 
Published: September 2006

AbstractInterleukin‐1 (IL‐1) and interleukin‐6 (IL‐6) have been reported to stimulate the release of corticotrophin‐releasing hormone (CRN) in vitro, the response being antagonized by the cyclo‐oxygenase inhibitor, indomethacin. The effects of cytokines on the other major ACTH‐releasing hormone, vasopressin (AVP), and the other neurohypophysial hormone, oxytocin, have been little studied, and the published data are conflicting. We have therefore used a previously validated rat hypothalamic expiant model to evaluate whether IL‐1β and IL‐6 can directly activate the AVP and oxytocin neurosecretory system. In addition, we have also investigated the effects of inhibition of cyclo‐oxygenase (CO) and lipoxygenase (LO) activities on the stimulated release of AVP and oxytocin by means of a series of antagonists, including a specific LO pathway inhibitor. The static rat hypothalamic incubation system used involves fresh hypothalamic expiants with consecutive 20‐min incubations, and estimation of AVP and oxytocin concentrations in the medium by specific and sensitive radioimmuno‐assays. It was found that IL‐1β produced a dose‐dependent increase in the release of AVP and oxytocin at doses of 10 and 100 U/ml (P<0.005). Only at the higher dose of 100 U/ml was IL‐6 able to increase significantly AVP and oxytocin release (P<0.05). These stimulatory effects of IL‐1β and IL‐6 were blocked by cyclo‐oxygenase inhibitors, indomethacin (28 μM) and ibuprofen (100 nM), but not by the lipooxygenase inhibitor, BW A4C (10 μg/ml), suggesting that prostaglandins are involved in this process. Thus, cytokines are clearly able to modulate the neurohypophysial system in vitro, the effects probably being mediated by cyclo‐oxygenase products.
Photoperiodically‐lnduced Cycles in the Secretion of Prolactin in Hypothalamo‐Pituitary Disconnected Rams: Evidence for Translation of the Melatonin Signal in the Pituitary Gland
Authors: Lincoln G. A. , Clarke I. J. 
Published: September 2006

AbstractLong term changes in the secretion of prolactin were monitored in groups of hypothalamo‐pituitary disconnected rams (HPD rams, n = 8) and control rams (HPD sham‐operated and unoperated, n = 8) while exposed to an artificial lighting regimen of alternating 16‐weekly periods of long days (16L : 8D) and short days (8L : 16D) for 72 weeks, and during a treatment with subcutaneous constant‐release implants of melatonin under long days. The HPD rams showed all the clinical characteristics of complete pituitary disconnection (diabetes insipidus, gonadal regression and slight obesity), and were unresponsive to a range of provocation tests (exposure to a barking sheep dog, cannulation of the jugular vein, injection of serotonin and NMDA) which caused acute changes in the blood plasma concentrations of prolactin in the controls. Nevertheless, there was a clearly defined cycle in the blood concentrations of prolactin in the HPD rams related to the imposed lighting regimen with values 10‐fold higher under long days compared to short days (HPD mean ± SEM: 90.1 ± 24.7 vs 9.4 ± 2.0 μl, long vs short day respectively, P < 0.001). The temporal pattern was very similar to that observed in the controls, although the concentrations of prolactin were higher in the HPD rams and more variable (control mean ± SEM: 55.6 ± 3.6 vs 3.0±0.5 μl, long vs short day, P < 0.001). There was a corresponding cycle in the growth and moulting of the wool in the HPD rams consistent with a biological response to the photoperiodically‐induced changes in the secretion of prolactin. The diurnal rhythm in the blood concentrations of prolactin was absent in the HPD rams, but there was a normal rhythm in the secretion of melatonin. The treatment of the animals with constant‐release implants of melatonin under long days caused a marked decrease in the blood concentrations of prolactin in both the HPD and control rams. The overall conclusion is that the endogenously generated daily melatonin signal which encodes daylength acts directly in the pituitary gland to mediate the effects of photo‐period on the secretion of prolactin. The photo‐period transduction pathway thus by‐passes the hypothalamus.
Selective Enhancement of an A Type Potassium Current by Dexamethasone in a Corticotroph Cell Line
Authors: Pennington Anne J. , Kelly John S. , Antoni Ferenc A. 
Published: September 2006

AbstractPerforated patch recording was used to examine the effect of the synthetic steroid dexamethasone on the whole cell potassium (K+) current, in the mouse corticotroph tumour cell line AtT20/D16‐16. In 15 out of 52 control cells (29%) there was a rapidly‐activating, rapidly‐ inactivating K+ current of the A type, the amplitude of which was strongly dependent on the holding potential in use prior to its activation by depolarising voltage pulses, and which was blocked by 1 mM 4‐aminopyridine (4‐AP, n = 5). The effect of dexamethasone (100nM, 2h, 37°C) was that the A current increased in prevelance (24 out of 31 cells, 77%), lost its dependence on holding potential (over the range studied), and as a result became significantly larger than in controls, for certain voltage steps (peak A current density was 18.5 +2.4 pA/pF (n = 12) for control cells and 26.3 ± 3.9 pA/pF (n = 18) for dexamethasone treated cells, for a step to +30mV from ‐60mV, values are mean ± SEM). All cells exhibited a slowly‐activating, sustained K+ current, which was unaffected by changes in the holding potential, unaffected by 4‐AP and consisted of at least 3 components: one blocked by 30 mM tetraethylammonium(TEA) or 100 nM charybdotoxin (CTX); a second blocked by 100 nM apamin; and a third not blocked by TEA, CTX, apamin, clofilium (100 nM) or niflumic acid (0.1 mM). Dexamethasone produced no change in the slowly‐activating, sustained current nor in any of its individual components. The effect of dexamethasone on the A current was completely blocked by 0.1 mM puromycin, a protein synthesis blocker, while puromycin alone did not affect the size or frequency of the A current, nor alter the slowly‐activating, sustained current. Secretion studies using 4‐AP confirmed that the A current has a role in stimulated adrenocorticotrophic hormone (ACTH) secretion. In summary, AtT20 cells contain at least four types of K+ current: an A current and 3 currents contributing to the slowly‐activating current. Selective enhancement of the A current by dexamethasone, shown here to require synthesis of new protein, is one of the mechanisms whereby glucocorticoids exert inhibitory control on ACTH secretion.
Localization of Pituitary Adenylate Cyclase‐Activating Polypeptide (PACAP) in the Hypothalamus‐Pituitary System in Rats: Light and Electron Microscopic Immunocytochemical Studies
Authors: Kimura Shigeharu , Ohshige Yoshimi , Lin Liping , Okumura Tadashi , Yanaihara Chizuko , Yanaihara Noboru , Shiotani Yahe 
Published: September 2006

AbstractThe localization of pituitary adenylate cyclase‐activating polypeptide (PACAP) in the hypothalamus‐pituitary system in rats was examined in light and electron microscopic immunocytochemistry using a specific antiserum to synthetic PACAP 1–38 (R0831). In light microscopic study, intensely PACAP‐immunostained perikarya were observed in the supraoptic and paraventricular magnocellular nucleus in the hypothalamus. In the median eminence, many immunoreactive nerve fibers were observed in the internal layer, but a few immunoreactive terminals were noticed in the external layer. In the pituitary gland, numerous immunoreactive nerve fibers were observed in the posterior lobe. In the intermediate lobe, moderately immunostained cells were observed, but in the anterior lobe no immunostained cells were noticed. In electron microscopic study, PACAP‐immunoreactivity was examined by avidin‐biotin peroxidase complex method. In the perikarya of the supraoptic and paraventricular magnocellular nucleus, DAB‐reaction products were distributed diffusely in the cytoplasmic matrix, frequently attaching to the rough‐surfaced endoplasmic reticulum. In the nerve terminals of the posterior lobe, reaction products were observed among the secretory granules, but sometimes upon them. In the cells of the intermediate lobe, reaction products were also distributed in the cytoplasmic matrix.