Experimental Limits on Solar Reflected Dark Matter with a New Approach on Accelerated-Dark-Matter-Electron Analysis in Semiconductors.

Recently a dark matter-electron (DM-electron) paradigm has drawn much attention. Models beyond the standard halo model describing DM accelerated by high energy celestial bodies are under intense examination as well. In this Letter, a velocity components analysis (VCA) method dedicated to swift analysis of accelerated DM-electron interactions via semiconductor detectors is proposed and the first HPGe detector-based accelerated DM-electron analysis is realized. Utilizing the method, the first germanium based constraint on sub-GeV solar reflected DM-electron interaction is presented with the 205.4 kg·day dataset from the CDEX-10 experiment. In the heavy mediator scenario, our result excels in the mass range of 5-15 keV/c^{2}, achieving a 3 orders of magnitude improvement comparing with previous semiconductor experiments. In the light mediator scenario, the strongest laboratory constraint for DM lighter than 0.1 MeV/c^{2} is presented. The result proves the feasibility and demonstrates the vast potential of the VCA technique in future accelerated DM-electron analyses with semiconductor detectors.

[Construction and validation of a nomogram model of early related factors for hepatic insufficiency after hemihepatectomy].

Objectives: To investigate the early related factors for hepatic insufficiency after hemihepatectomy and to construct and validate a nomogram model. Methods: This was a retrospective cohort study.There were 207 patients with liver tumor who underwent hemihepatectomy in the Department of Hepatobiliary Surgery,Cancer Hospital,Chinese Academy of Medical Sciences from October 2016 to December 2022. Using the random number method,patients were randomly divided into a model group(n=166) and a validation group(n=41) according to an 4︰1 ratio. There were 118 males and 48 females in the modeling group,with an age (M(IQR)) of 59.0(13.3) years (range: 22.0 to 81.0 years),42 patients in the group with postoperative liver insufficiency and 124 patients in the group without postoperative liver insufficiency. There were 32 males and 9 females in the validation group, with an age of 54.0(19.0) years (rang: 25.0~81.0 years). The first results of the peripheral blood test of patients within 24 hours after surgery were collected,and the independent related factors for incomplete postoperative liver function were determined by multivariate Logistic regression analysis,and related factors of postoperative incomplete liver function were screened by best subset selection. A nomogram model of the risk of postoperative hepatic insufficiency after hemihepatectomy was constructed using R software,followed by internal and external validation of the model. Results: Multivariate logistic regression analysis showed that elevated D-dimer level and decreased antithrombin Ⅲ (AT-Ⅲ) activity within 24 hours after surgery were independent related factors for the development of postoperative hepatic insufficiency in hemihepatectomized patients. The results of the best subset selection showed that ALT,D-dimer, and AT-Ⅲ activity levels within 24 hours postoperatively were the most relevant factors for postoperative hepatic insufficiency. The R software was applied to build a nomogram prediction model based on the above three indicators in the model set,and the receiver operating characteristic(ROC) curve of the model showed an area under the curve of 0.803 and the calibration curve showed a U-index of -0.012 for the model(P=0.977). The results of the clinical decision analysis and the clinical impact curve indicated that the model had good clinical utility. The internal validation results of the Bootstrap method suggested that the model had reasonable consistency. The area under the ROC curve of the validation group model was 0.806,suggesting that the model had a good generalization prediction ability. Conclusions: The levels of ALT,D-dimer,and AT-Ⅲ activity within 24 hours after hemihepatectomy are valuable indicators for predicting liver insufficiency after hemihepatectomy. The nomogram model is reliable and can be used as an indicator for close postoperative monitoring.

Constraints on Sub-GeV Dark Matter-Electron Scattering from the CDEX-10 Experiment.

We present improved germanium-based constraints on sub-GeV dark matter via dark matter-electron (χ-e) scattering using the 205.4 kg·day dataset from the CDEX-10 experiment. Using a novel calculation technique, we attain predicted χ-e scattering spectra observable in high-purity germanium detectors. In the heavy mediator scenario, our results achieve 3 orders of magnitude of improvement for m_{χ} larger than 80 MeV/c^{2} compared to previous germanium-based χ-e results. We also present the most stringent χ-e cross-section limit to date among experiments using solid-state detectors for m_{χ} larger than 90 MeV/c^{2} with heavy mediators and m_{χ} larger than 100 MeV/c^{2} with electric dipole coupling. The result proves the feasibility and demonstrates the vast potential of a new χ-e detection method with high-purity germanium detectors in ultralow radioactive background.

Exotic Dark Matter Search with the CDEX-10 Experiment at China's Jinping Underground Laboratory.

A search for exotic dark matter (DM) in the sub-GeV mass range has been conducted using 205 kg day data taken from a p-type point contact germanium detector of the CDEX-10 experiment at China's Jinping underground laboratory. New low-mass dark matter searching channels, neutral current fermionic DM absorption (χ+A→ν+A) and DM-nucleus 3→2 scattering (χ+χ+A→ϕ+A), have been analyzed with an energy threshold of 160 eVee. No significant signal was found; thus new limits on the DM-nucleon interaction cross section are set for both models at the sub-GeV DM mass region. A cross section limit for the fermionic DM absorption is set to be 2.5×10^{-46} cm^{2} (90% C.L.) at DM mass of 10 MeV/c^{2}. For the DM-nucleus 3→2 scattering scenario, limits are extended to DM mass of 5 and 14 MeV/c^{2} for the massless dark photon and bound DM final state, respectively.

Direct Detection Constraints on Dark Photons with the CDEX-10 Experiment at the China Jinping Underground Laboratory.

We report constraints on the dark photon effective kinetic mixing parameter (κ) with data taken from two p-type point-contact germanium detectors of the CDEX-10 experiment at the China Jinping Underground Laboratory. The 90% confidence level upper limits on κ of solar dark photon from 205.4 kg-day exposure are derived, probing new parameter space with masses (m_{V}) from 10 to 300 eV/c^{2} in direct detection experiments. Considering dark photon as the cosmological dark matter, limits at 90% confidence level with m_{V} from 0.1 to 4.0 keV/c^{2} are set from 449.6 kg-day data, with a minimum of κ=1.3×10^{-15} at m_{V}=200 eV/c^{2}.

Constraints on Spin-Independent Nucleus Scattering with sub-GeV Weakly Interacting Massive Particle Dark Matter from the CDEX-1B Experiment at the China Jinping Underground Laboratory.

We report results on the searches of weakly interacting massive particles (WIMPs) with sub-GeV masses (m_{χ}) via WIMP-nucleus spin-independent scattering with Migdal effect incorporated. Analysis on time-integrated (TI) and annual modulation (AM) effects on CDEX-1B data are performed, with 737.1 kg day exposure and 160 eVee threshold for TI analysis, and 1107.5 kg day exposure and 250 eVee threshold for AM analysis. The sensitive windows in m_{χ} are expanded by an order of magnitude to lower DM masses with Migdal effect incorporated. New limits on σ_{χN}^{SI} at 90% confidence level are derived as 2×10^{-32}∼7×10^{-35} cm^{2} for TI analysis at m_{χ}∼50-180 MeV/c^{2}, and 3×10^{-32}∼9×10^{-38} cm^{2} for AM analysis at m_{χ}∼75 MeV/c^{2}-3.0 GeV/c^{2}.

Search for Light Weakly-Interacting-Massive-Particle Dark Matter by Annual Modulation Analysis with a Point-Contact Germanium Detector at the China Jinping Underground Laboratory.

We present results on light weakly interacting massive particle (WIMP) searches with annual modulation (AM) analysis on data from a 1-kg mass p-type point-contact germanium detector of the CDEX-1B experiment at the China Jinping Underground Laboratory. Datasets with a total live time of 3.2 yr within a 4.2-yr span are analyzed with analysis threshold of 250 eVee. Limits on WIMP-nucleus (χ-N) spin-independent cross sections as function of WIMP mass (m_{χ}) at 90% confidence level (C.L.) are derived using the dark matter halo model. Within the context of the standard halo model, the 90% C.L. allowed regions implied by the DAMA/LIBRA and CoGeNT AM-based analysis are excluded at >99.99% and 98% C.L., respectively. These results correspond to the best sensitivity at m_{χ}<6 GeV/c^{2} among WIMP AM measurements to date.

Limits on Light Weakly Interacting Massive Particles from the First 102.8 kg×day Data of the CDEX-10 Experiment.

We report the first results of a light weakly interacting massive particles (WIMPs) search from the CDEX-10 experiment with a 10 kg germanium detector array immersed in liquid nitrogen at the China Jinping Underground Laboratory with a physics data size of 102.8 kg day. At an analysis threshold of 160 eVee, improved limits of 8×10^{-42} and 3×10^{-36} cm^{2} at a 90% confidence level on spin-independent and spin-dependent WIMP-nucleon cross sections, respectively, at a WIMP mass (m_{χ}) of 5 GeV/c^{2} are achieved. The lower reach of m_{χ} is extended to 2 GeV/c^{2}.

Involvement of protein kinase C and intracellular Ca2+ in goldfish brain somatostatin-28 inhibitory action on growth hormone release in goldfish.

Goldfish brain somatostatin-28 (gbSS-28) is present in brain and pituitary tissues of goldfish. We assessed whether gbSS-28 targets Ca(2+) and/or protein kinase C (PKC)-dependent signaling cascades in inhibiting growth hormone (GH) release. gbSS-28 decreased basal GH release from primary cultures of dispersed goldfish pituitary cells and intracellular free calcium levels ([Ca(2+)](i)) in goldfish somatotropes. gbSS-28 partially reduced [Ca(2+)](i) and GH responses induced by two endogeneous gonadotropin-releasing hormones (GnRHs), salmon (s)GnRH and chicken (c)GnRH-II. Furthermore, gbSS-28 reduced GH increases and abolished [Ca(2+)](i) elevations elicited by two PKC activators, tetradecanoyl 4beta-phorbol-13-acetate and dioctanyl glycerol. The PKC inhibitors Gö6976 and Bis II abolished [Ca(2+)](i) responses to PKC activators, but only attenuated GnRH-induced increases in [Ca(2+)](i) and did not alter basal [Ca(2+)](i). In cells pretreated with Bis II, gbSS-28 further reduced basal [Ca(2+)](i). Our results suggest that gbSS-28 inhibits GnRH-induced GH release in part by attenuating PKC-mediated GnRH [Ca(2+)](i) signals. gbSS-28 reduces basal GH release also via reduction in [Ca(2+)](i) but PKC is not involved in this regard.

Left atrial enlargement induced by pure mitral regurgitation: time frame in a new swine model.

BACKGROUND: Atrial enlargement occurs in patients with significant mitral regurgitation. However, the time frame of the development of atrial enlargement induced by mitral regurgitation remains unknown. METHODS: Fourteen Lanyu miniature pigs (age = 6.6 ± 0.9 months) were studied. Mitral regurgitation was created by placing a predefined hole on the middle scallop of the posterior mitral leaflet under cardiopulmonary bypass. The parasternal long-axis atrial dimension was measured by transthoracic echocardiographic examinations. RESULTS: All animals exhibited grade 3 mitral regurgitation immediately after surgery. Seven pigs expired within 2 weeks after the operation [technical complications (n = 1), acute cardiac tamponade (n = 1), and acute and subacute heart failure (n = 5)]. Seven pigs remained alive at a mean follow-up of 7.7 ± 2.1 months. The left atrial diameter indices of the 7 pigs increased significantly at 1 month (33.1 ± 8.6 mm, p = 0.018) and 3 months (41.3 ± 12.6 mm, p = 0.018) after surgery compared with baseline values (22.8 ± 5.2 mm), and the left atrial diameter index increased significantly at 3 months compared to 1 month (p = 0.018). CONCLUSIONS: Left atrial enlargement develops rapidly and progresses after the creation of significant pure mitral regurgitation.

Multifactorial control of reproductive and growth axis in male goldfish: Influences of GnRH, GnIH and thyroid hormone.

Reproduction and growth are under multifactorial control of neurohormones and peripheral hormones. This study investigated seasonally related effects of GnIH, GnRH, and T3 on the reproductive and growth axis in male goldfish at three stages of gonadal recrudescence. The effects of injection treatments with GnRH, GnIH and/or T3 were examined by measuring serum LH and GH levels, as well as peripheral transcript levels, using a factorial design. As expected, GnRH elevated serum LH and GH levels in a seasonally dependant manner, with maximal elevations of LH in late stages of gonadal recrudescence (Spring) and maximal increases in GH in the regressed gonadal stage (Summer). GnIH injection increased serum LH and GH levels only in fish at the regressed stage but exerted both stimulatory and inhibitory effects on GnRH-induced LH responses depending on season. T3 treatment mainly had stimulatory effects on circulating LH levels and inhibitory effects on serum GH concentrations. In the liver and testes, we observed seasonal differences in thyroid receptors, estrogen receptors, vitellogenin, follicle-stimulating hormone receptor, aromatase and IGF-I transcript levels that were tissue- and sex-specific. Generally, there were no clear correlation between circulating LH and GH levels and peripheral transcript levels, presumably due to time-related response and possible direct interaction of GnRH and GnIH at the level of liver and testis. The results support the hypothesis that GnRH and GnIH are important components of multifactorial mechanisms that work in concert with T3 to regulate reciprocal control of reproduction and growth in goldfish.

Growth hormone and insulin-like growth factor of naked carp (Gymnocypris przewalskii) in Lake Qinghai: expression in different water environments.

Here, we report the cloning and characterization of growth hormone (GH), insulin-like growth factor-I (IGF-I) and IGF-II from naked carp (Gymnocypris przewalskii), a native teleost fish of Lake Qinghai in the Qinghai-Tibet Plateau of China. The GH of naked carp encodes for a predicted amino acid sequence showing identities of 63%, 63%, 91% and 94% with cherry salmon, rainbow trout, zebrafish and grass carp, respectively. Compared to common carp and goldfish, evolutionary analysis showed that genome duplication has had less influence on the relaxation of purifying selection in the evolution of naked carp GH. Sequence analysis of naked carp IGF-I (ncIGF-I) and ncIGF-II showed a high degree of homology with known fish IGF-I and IGF-II. To investigate effects of salinity and ionic composition of the aquatic environment on the GH-IGF axis in naked carp, male fish held in river water were assigned randomly to 4 groups: RW (river-water), RW+Na (NaCl in RW), RW+Mg (MgCl(2) in RW) and LW (lake-water) groups. The concentrations of Na(+) in RW+Na and Mg(2+) in RW+Mg were equal to the concentrations of these ions in lake-water. After 2 days of exposure, the plasma IGF-I levels in the RW+Na and LW groups were significantly higher than the control group (RW), and the plasma GH levels of the LW group were also significantly higher than the RW group. The somatostatin (SS) levels in the hypothalamus significantly increased in the RW+Na group. After 5 days of exposure, these hormone levels did not differ significantly among groups. These results indicate that while the plasma GH and IGF-I levels are osmosensitive, the absence of a change in GH secretion in RW+Na might be partly due to a transiently increased release of hypothalamic SS induced by the stress of neutral-saline water. This is the first report of a salinity-induced increase of GH-IGF-I circulating levels in Cypriniformes.

The effects of GABA agonists on glutamic acid decarboxylase, GABA-transaminase, activin, salmon gonadotrophin-releasing hormone and tyrosine hydroxylase mRNA in the goldfish (Carassius auratus) neuroendocrine brain.

GABA plays a pivotal role in reproduction by regulating luteinising hormone (LH) release from the anterior pituitary. Current evidence indicates that there is a prominent stimulatory effect of GABA on LH release in teleost fish which results from enhanced gonadotrophin-releasing hormone (GnRH) release and decreased dopamine turnover in the brain and pituitary. We hypothesised that there may be additional mechanisms underlying LH release in goldfish and investigated the relative mRNA levels of GABA synthesising enzymes (GAD65 and GAD67), degrading enzyme (GABA-T), activin betaa and betab, salmon GnRH (sGnRH), and tyrosine hydroxylase (TH) with the real-time reverse transcriptase-polymerase chain reaction after GABA agonist treatment. Sexually regressed female goldfish were i.p. injected with either the GABA(A) agonist muscimol (1 microg/g body weight) or the GABA(B) agonist baclofen (10 microg/g body weight). Both agonists significantly increased serum LH after 6 h. Muscimol decreased GAD65 (approximately ten-fold), GABA-T (approximately 15-fold) and TH (approximately three-fold) mRNA in the telencephalon. Baclofen significantly reduced GAD67 (approximately two-fold) and GABA-T (approximately two-fold) mRNA levels in the hypothalamus. Activin betaa, but not activin betab, steady-state mRNA was increased approximately three- to four-fold in both the hypothalamus and telencephalon after baclofen treatment. There was no change in sGnRH mRNA levels in either tissue after GABA agonist treatment. We show that the GABA(A) and GABA(B) receptor agonists have differing and rapid effects on gene transcription in the goldfish neuroendocrine brain and, by affecting specific targets, we identify putative genomic mechanisms underlying GABA-stimulated LH release in fish.

Design, microfabrication, and analysis of micrometer-sized cylindrical ion trap arrays.

A description of the design and microfabrication of arrays of micrometer-scale cylindrical ion traps is offered. Electrical characterization and initial ion trapping experiments with a massively parallel array of 5 microm internal radius (r(0)) sized cylindrical ion traps (CITs) are also described. The ion trap, materials, and design are presented and shown to be critical in achieving minimal trapping potential while maintaining minimal power consumption. The ion traps, fabricated with metal electrodes, have inner radii of 1, 2, 5, and 10 microm and range from 5 to 24 microm in height. The electrical characteristics of packaged ion trap arrays were measured with a vector network analyzer. The testing focused on trapping toluene (C(7)H(8)), mass 91, 92, or 93 amu, in the 5 microm sized CITs. Ions were formed via electron impact ionization and were ejected by turning off the rf voltage applied to the ring electrode; a current signal was collected at this time. Optimum ionization and trapping conditions, such as a sufficient pseudopotential well and high ionization to ion loss rate ratio (as determined by simulation), proved to be difficult to establish due to the high device capacitance and the presence of exposed dielectric material in the trapping region. However, evidence was obtained suggesting the trapping of ions in 1%-15% of the traps in the array. These first tests on micrometer-scale CITs indicated the necessary materials and device design modifications for realizing ultrasmall and low power ion traps.

Ultracytochemical localization of glucose-6-phosphatase in Chang rat hepatoma in vivo and in vitro.

The standard lead precipitation method was used for ultracytochemical localization of glucose-6-phosphatase (G-6-Pase) in the in vivo and in vitro forms of the Chang rat hepatoma and in the normal adult rat liver. Reaction product was visualized as very fine particulate within the cisternae of the nuclear envelope and endoplasmic reticulum. Cytochemically, the amount of the G-6-Pase reaction product in both forms of the tumor cells was obviously less than that in the normal hepatocytes. Apparently, the enzyme was not completely deleted from the hepatoma cells. The results supported some biochemical data of certain other hepatomas. The successful ultracytochemical localization of G-6-Pase in cultured hepatoma cells has not been reported previously.

Intracellular calcium involvement in pituitary adenylate cyclase-activating polypeptide stimulation of growth hormone and gonadotrophin secretion in goldfish pituitary cells.

The involvement of intracellular Ca(2+) stores and their regulatory mechanisms in mediating pituitary adenylate cyclase-activating polypeptide (PACAP) stimulation of growth hormone (GH) and maturational gonadotrophin (GTH-II) secretion from goldfish pituitary cells was investigated using a cell column perifusion system. Pretreatment with caffeine abolished the GH and GTH-II responses to PACAP. Dantrolene attenuated PACAP-elicited GTH-II release but did not affect the GH response, whereas ryanodine and 8-bromo-cADP ribose did not alter PACAP-induced GH and GTH-II release. Two endoplasmic/sarcoplasmic reticulum Ca(2+) ATPase (SERCA) inhibitors, thapsigargin and cyclopiazonic acid, augmented PACAP-induced GTH-II release; similarly, thapsigargin elevated GH responses to PACAP. Treatment with carbonyl cyanide m-chlorophenylhydrazone, a mitochondrial uncoupler, reduced PACAP-stimulated GH release; however, inhibition of the mitochondrial Ca(2+) uniport by Ru360 did not affect GH and GTH-II responses. The phosphatidyl inositol (PI)-specific phospholipase C (PLC) inhibitor ET-18-OCH(3) inhibited, whereas the phosphatidyl-choline (PC)-specific PLC inhibitor D609 enhanced, PACAP-stimulated GH and GTH-II responses. On the other hand, the IP(3) receptor blocker xestospongin D had no effect on PACAP-induced GTH-II response and potentiated the GH response. These results suggest that, despite some differences between GH and GTH-II cells, PACAP actions in both cell types generally rely on a caffeine-sensitive, but a largely ryanodine receptor-independent, mechanism. PC-PLC and some SERCA negatively modulate PACAP actions but mitochondrial Ca(2+) stores per se are not important. A novel PI-PLC mechanism, which does not involve the traditional IP(3)/Ca(2+) pathway, is also suggested.

Actions of two native GnRHs and protein kinase C modulators on goldfish pituitary cells. Studies on intracellular calcium levels and gonadotropin release.

Previous results indicate that the two native gonadotropin (GtH)-releasing hormones of the goldfish, sGnRH and cGnRHII, stimulate GtH secretion in an extracellular Ca2+ ([Ca2+]o) dependent manner. In the present study, sGnRH, cGnRHII, KCI and the protein kinase C (PKC) activators TPA and DiC8, stimulated increases in intracellular Ca2+ ([Ca2+]i) levels in goldfish pituitary cells. Testing in Ca(2+)-deficient medium abolished the [Ca2+]i responses to cGnRHII, TPA and KCI and attenuated responses to sGnRH and DiC8. These results are the first to demonstrate that in teleost pituitary cells both native GnRHs stimulate increases in [Ca2+]i levels via [Ca2+]o entry. sGnRH- and DiC8-stimulated increases in [Ca2+]i also appear to be partially due to mobilization of Ca2+ from intracellular stores. Other results are consistent with a role for PKC in mediating GnRH action especially extracellular Ca2+ entry. Firstly, the PKC inhibitor staurosporine decreased GnRH- and TPA-induced [Ca2+]i responses. Secondly, incubation with Ca(2+)-deficient medium attenuated TPA- and DiC8-stimulated GtH release. Thirdly, GtH release responses to PKC activators were enhanced and reduced by an agonist and an antagonist of Ca2+ channel function, respectively. However, differences in the sensitivity of DiC8- and TPA-elicited responses to manipulations of [Ca2+]o entry indicate that these two PKC activators may have different actions in the goldfish pituitary. A difference in action of the two GnRHs on mobilization of Ca2+ from intracellular stores is also indicated.

Dynamic actions of arachidonic acid and protein kinase C in pituitary stimulation by gonadotropin-releasing hormone.

The relative contributions of arachidonic acid (AA)- and protein kinase C-dependent pathways during the immediate LH response to short term stimulation by GnRH were analyzed in perifused anterior pituitary cells cultured on Cytodex beads. The LH response to a 2-min pulse of 10 nM GnRH was biphasic, with a rapid increase to an initial peak, followed by a second peak or shoulder before the gradual return to baseline release. Retinal, which inhibits activation of protein kinase C, reduced the total LH response to GnRH by 35-40% and advanced the termination of the response, but did not alter the height, position, or rate of onset of the initial LH peak. In contrast, pretreatment with the lipoxygenase inhibitor nordihydroguaiaretic acid decreased the total LH response to GnRH by 60%, reduced the magnitude and latency of the first LH peak, and shortened the duration of the response. Pretreatment with both retinal and nordihydroguaiaretic acid abolished the GnRH-induced LH release. Addition of 2-min pulses of AA induced LH responses of short duration that coincided with the first phase of GnRH-stimulated LH release. Application of 2-min pulses of either tetradecanoyl phorbol 13-acetate (TPA) or dioctanoyl glycerol generated LH responses with delayed onsets that corresponded to the second phase of the GnRH-induced response. The LH response to the combined action of AA and TPA approximated that induced by GnRH. These results suggest that mobilization and metabolism of AA are important in the rapid initial phase of the LH response to GnRH, and that activation of protein kinase C-dependent mechanisms participates in the maintenance of the LH response. During continuous perifusion with 10 nM GnRH, addition of 2-min pulses of 100 nM GnRH and 100 microM AA, but not 100 nM TPA, stimulated further increases in LH release. This suggests that during prolonged GnRH action, LH release is primarily maintained by protein kinase C-dependent mechanisms. The results of this study indicate that GnRH stimulation of LH release requires the coordinated actions of at least two major interrelated mechanisms, namely those activated by AA and/or its metabolites and those maintained by protein kinase C-dependent pathways.

Dopamine stimulates growth hormone release from the pituitary of goldfish, Carassius auratus, through the dopamine D1 receptors.

Previously, we have demonstrated that ip injection of apomorphine, a nonselective dopamine (DA) agonist, increases serum GH levels in the goldfish, suggesting a possible role of DA in GH regulation. In the present study, the effects of DA on GH release in the goldfish were further characterized using an in vitro perifusion system for pituitary fragments. DA increased GH release in a dose-dependent manner with an ED50 of 0.26 +/- 0.06 microM. SKF38393, a DA D1 agonist, mimicked the GH-releasing effect of DA with an ED50 of 0.41 +/- 0.12 microM. Stereoselectivity consistent with mammalian DA D1 systems was demonstrated for the GH response to SKF38393; only the (+)- but not (-)-enantiomer of SKF38393 induced a dose-dependent GH release. Two other D1 agonists, SKF77434 and SKF82958, were also found to have GH-releasing activity. In contrast, high doses (up to 1 microM) of the DA D2 agonists, bromocriptine and LY171555, did not affect basal GH levels. The receptor specificity for DA-stimulated GH release was further investigated by using D1 and D2 antagonists; the D1 antagonists SCH23390 and SKF83566 completely abolished the GH response to DA or the D1 agonist SKF38393, whereas the D2-specific antagonists domperidone and (-)-sulpiride were not effective in this respect. Taken together, the present study demonstrates that DA is stimulatory to GH release from the pituitary of goldfish, and its action is mediated through receptors resembling the mammalian DA D1 receptors. The apparent similarities of the DA D1 receptor pharmacology between the goldfish and the mammals also indicate that D1 receptor is highly conserved during vertebrate evolution.