Biomedical subjects

O K Park

Publications and source records attributed to O K Park.

At least 19 recordsLinked to original sources

PubMed2000

Dimer stability as a determinant of differential DNA binding activity of Stat3 isoforms.

Stat3alpha and Stat3beta are two Stat3 isoforms with marked quantitative differences in their DNA binding activities. To examine the molecular basis of the differential DNA binding activities, we measured DNA binding strength and dimer stability, two possible mechanisms responsible for these differences. Stat3alpha and Stat3beta showed no difference in DNA binding strength, i.e. they had similar association and dissociation rates for DNA binding. However, competition analyses performed with dissociating reagents including an anti-phosphotyrosine antibody, SH2 domain protein, and a phosphopeptide demonstrated that Stat3beta dimers are more stable than Stat3alpha dimers. We report here that dimer stability of activated forms plays a critical role in determining DNA binding activity of Stat3 isoforms. We found that C-terminal deletions of Stat3alpha increased both DNA binding activity and dimer stability of Stat3alpha. Our findings suggest that the acidic C-terminal region of Stat3alpha does not interfere with the DNA binding of activated Stat3alpha dimers, but destabilizes the dimeric forms of Stat3alpha. We propose that dimer stability described in vitro may be the underlying mechanism of in vivo stability of activated Stat3 proteins, regulating dephosphorylation of tyrosine 705.

Animals↗

PubMed2000

In vivo determination of substrate specificity of hepatitis C virus NS3 protease: genetic assay for site-specific proteolysis.

Hepatitis C virus (HCV) NS3 protease is responsible for the processing of the viral polyprotein and is considered as a primary target for the development of anti-HCV therapy. We have developed a genetic method in yeast to screen for good substrate sequences of the NS3 protease. A library of fusion proteins was constructed with a transcription factor, GAL4, linked to the intracellular domain of an integral membrane protein, STE2, by a randomized protease substrate sequence. In yeast cells expressing NS3 protease, the substrate sequences in the fusion proteins were specifically recognized and cleaved. This cleavage resulted in the release of GAL4 from the cytoplasmic membrane and the subsequent activation of reporter genes by GAL4, which was detected by the growth of yeast cells on selective media. Based on the analysis of 69 isolated substrate sequences, a consensus sequence was deduced: (Glu/Asp)-X-Val-Val-(Leu/Pro)-Cys / (Ser/Ala), with the scissile bond being located between Cys and Ser or Ala and X not being determined. This is largely consistent with the previous results obtained by biochemical methods. An oligopeptide containing the deduced sequence was highly efficiently cleaved in vitro by the purified NS3 protease. These data demonstrated that the present genetic method could be used as an efficient tool for the in vivo determination of substrate specificity of proteases.

Amino Acids↗

PubMed2000

Identification of a new active site for autocatalytic processing of penicillin acylase precursor in Escherichia coli ATCC11105.

Penicillin acylase (PA) from Escherichia coli ATCC11105 is a periplasmic heterodimer consisting of a 24 kDa small subunit and a 65 kDa large subunit. It is synthesized as a single 96 kDa precursor and then matures to functional PA via a posttranslational processing pathway. The GST-PA fusion protein expression system was established for monitoring the precursor PA processing in vitro. The purified PA precursor was processed into mature PA the same way as in vivo, but pH dependently. From the primary sequence analysis, we identified a putative conserved lysine residue (K299) responsible for the pH dependent processing. The substitution of K299 residue by site-directed mutagenesis affected both the enzyme activity and the precursor PA processing in vivo. Furthermore, it was shown that the processing rates of wild-type and mutant precursor PAs depended on the pKa values of their side chain R group. These results demonstrated that the lysine residue (K299) was involved in the precursor processing of PA together with N-terminal serine residue (S290) of the large subunit.

Amino Acid Sequence↗

PubMed2000

The water extract of Jagamchotang protects the ischemia/reperfusion-induced cytotoxicity of rat neonatal myocardial cells via generation of nitric oxide.

Jagamchotang has been used for treatment of ischemic myocardial diseases in Chinese traditional medicine. However, little is known about the mechanism by which Jagamchotang rescues myocardial cells from ischemic damages. To elucidate the protective mechanisms, the effects of Jagamchotang on ischemia/reperfusion-induced cytotoxicity and generation of nitric oxide (NO) are investigated in primary neonatal myocardial cells. Ischemia/reperfusion itself induces severe myocardial cell death in vitro. However, treatment of the cells with Jagamchotang significantly reduces both ischemia/reperfusion-induced myocardial cell death and LDH release. In addition, pretreatment of Jagamchotang before reperfusion recovers the lose of beating rates after ischemia/reperfusion. For a while, the water extract of Jagamchotang stimulates myocardial cells in ischemic condition to produce nitric oxide (NO) in a dose dependent manner and it protects the damage of myocardial cells. Furthermore, the protective effects of the water extract of Jagamchotang is mimicked by treatment of sodium nitroprusside, an exogenous NO donor. NG-monomethyi-L-argine (NGMMA), a specific inhibitor of nitric oxide synthase (NOS), significantly blocks the protective effects of Jagamchotang on the cells after ischemia/reperfusion. Taken together, we suggest that the protective effects of Jagamchotang against ischemia/reperfusion-induced myocardial damages may be mediated by NO production during ischemic condition.

Animals↗

PubMed2000

Initial and late results of Freedom coronary stent.

OBJECTIVES: Initial and late results after implantation of Freedom stents, a balloon expandable stainless steel coil stents were evaluated. METHODS: From Jun. 1996 to Nov. 1997, we implanted 123 Freedom stents in 122 lesions in 117 patients and performed follow-up coronary angiograms at 7.0 +/- 3.6 months after stents placement. Clinical courses after stenting and follow-up coronary angiographic findings were evaluated. Comparison of clinical, angiographic, and procedural factors according to the presence or absence of restenosis was performed. RESULTS: In 117 patients who underwent stents implantation, major complications were not observed. Follow-up coronary angiograms were performed in 47 stents in 41 patients (35%). Among 47 stents, angiographic significant restenosis (percent diameter stenosis > 50%) was observed in 13 (28%). Mean age in 41 patients was 59 +/- 9 years, with 27 male patients (66%). Indications for stents implantation were de novo lesions in 18 (38%), suboptimal results after PTCA in 18 (38%), bail-out lesions in 4 (9%) and restenotic lesions in 7 (15%). Lesion types by AHA/ACC classification were A in 1 (1%), B1 in 10 (21%), B2 in 17 (36%), and C in 19 (40%). Average lesion length was 13.7 +/- 9.0 mm, stent diameter 3.0 +/- 0.3 mm, and stent length 24.6 +/- 9.0 mm. There were no significant differences of the clinical, angiographic, and procedural characteristics according to the presence or absence of restenosis. CONCLUSION: Freedom coronary stents implantation is safely performed in various morphology of coronary lesions and no significant predictive factors on restenosis in follow-up coronary angiogram were observed.

Aged↗

PubMed1999

Selection of Drosophila genes encoding secreted and membrane proteins.

With the use of a yeast-based signal sequence trap (YSST) method, we screened a Drosophila cDNA library to isolate genes encoding secreted and membrane proteins. Of the 136 unique cDNA clones sequenced, 11 clones (8.1%) are identical to previously known Drosophila genes, 18 clones (13.2%) are homologous to other genes identified in various organisms, and 91 clones (66.9%) are novel. Most of these genes are secreted or membrane proteins, or appear to contain putative signal sequences at their amino termini. This indicates that YSST is an effective tool for the isolation and analysis of Drosophila genes that play roles in intercellular communication.

Animals↗

PubMed1999

Selection of Arabidopsis genes encoding secreted and plasma membrane proteins.

Secreted and plasma membrane proteins play crucial roles in a variety of physiological and developmental processes of multicellular organisms. Systematic cloning of the genes encoding these proteins is therefore of general interest. An effective method of trapping signal sequences was first described by Tashiro et al. (1993), and a similar yet more efficient method was reported by Klein et al. (1996) and Jacobs et al. (1997). In this study, we carried out the latter yeast-based signal sequence trap to clone genes from Arabidopsis thaliana encoding secreted and plasma membrane proteins. Of 144 sequenced cDNA clones, 18% are identical to previously cloned Arabidopsis thaliana genes, 12% are homologous to genes identified from various organisms, and 46% are novel. All of the isolated genes identical or homologous to previously reported genes are either secreted or plasma membrane proteins, and the remaining novel genes appear to contain functional signal sequences based on computer-aided sequence analysis. The full-length cDNA clones of one homologous gene and another novel gene were isolated and sequenced. The deduced amino acid sequences suggest that the former encodes a secreted protein, and the latter encodes a type 1 membrane protein. These results indicate that the signal sequence trap method is effective and useful for the isolation of plant genes encoding secreted and plasma membrane proteins.

Amino Acid Sequence↗

PubMed1999

Metal-catalyzed oxidation of phenylalanine-sensitive 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase from Escherichia coli: inactivation and destabilization by oxidation of active-site cysteines.

The in vitro instability of the phenylalanine-sensitive 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase [DAHPS(Phe)] from Escherichia coli has been found to be due to a metal-catalyzed oxidation mechanism. DAHPS(Phe) is one of three differentially feedback-regulated isoforms of the enzyme which catalyzes the first step of aromatic biosynthesis, the formation of DAHP from phosphoenolpyruvate and D-erythrose-4-phosphate. The activity of the apoenzyme decayed exponentially, with a half-life of about 1 day at room temperature, and the heterotetramer slowly dissociated to the monomeric state. The enzyme was stabilized by the presence of phosphoenolpyruvate or EDTA, indicating that in the absence of substrate, a trace metal(s) was the inactivating agent. Cu2+ and Fe2+, but none of the other divalent metals that activate the enzyme, greatly accelerated the rate of inactivation and subunit dissociation. Both anaerobiosis and the addition of catalase significantly reduced Cu2+-catalyzed inactivation. In the spontaneously inactivated enzyme, there was a net loss of two of the seven thiols per subunit; this value increased with increasing concentrations of added Cu2+. Dithiothreitol completely restored the enzymatic activity and the two lost thiols in the spontaneously inactivated enzyme but was only partially effective in reactivation of the Cu2+-inactivated enzyme. Mutant enzymes with conservative replacements at either of the two active-site cysteines, Cys61 or Cys328, were insensitive to the metal attack. Peptide mapping of the Cu2+-inactivated enzyme revealed a disulfide linkage between these two cysteine residues. All results indicate that DAHPS(Phe) is a metal-catalyzed oxidation system wherein bound substrate protects active-site residues from oxidative attack catalyzed by bound redox metal cofactor. A mechanism of inactivation of DAHPS is proposed that features a metal redox cycle that requires the sequential oxidation of its two active-site cysteines.

3-Deoxy-7-Phosphoheptulonate Synthase↗

PubMed1998

Isolation of an extragenic suppressor of the rna1-1 mutation in Saccharomyces cerevisiae.

The small GTPase Ran is essential for nucleocytoplasmic transport of macromolecules. In the yeast Saccharomyces cerevisiae, Rna1p functions as a Ran-GTPase activating protein (RanGAP1). Strains carrying the rna1-1 mutation exhibit defects in nuclear transport and, as a consequence, accumulate precursor tRNAs. We have isolated two recessive suppressors of the rna1-1 mutation. Further characterization of one of the suppressor mutations, srn10-1, reveals that the mutation (i) can not bypass the need for Rna1p function and (ii) suppresses the accumulation of unspliced pre-tRNA caused by rna1-1. The SRN10 gene is not essential for cell viability and encodes an acidic protein (pI = 5.27) of 24.8 kDa. Srn10p is located in the cytoplasm, as determined by indirect immunofluorescence microscopy. Two-hybrid analysis reveals that there is a physical interaction between Srn10p and Rna1p in vivo. Our results identify a protein that interacts with the yeast RanGAP1.

Amino Acid Sequence↗

PubMed1998

Immunohistochemical study of 3beta-hydroxysteroid dehydrogenase/delta5-delta4 isomerase in the rat cardiovascular system.

The enzyme complex 3beta-hydroxysteroid dehydrogenase (3beta-HSD) is involved in the biosynthesis of all classes of active steroids. It is known that the enzymatic activity of 3beta-HSD is present not only in classical steroidogenic tissues, but also in many peripheral tissues including cardiac tissue. To determine whether 3beta-HSD is present in rat non-steroidogenic tissues, we examined cardiovascular tissues including the ventricle, atrium, aortic arch, abdominal aorta, and inferior vena cava by immunohistochemistry and Western blotting using polyclonal antibody raised against a synthetic peptide of human placental 3beta-HSD. By Western blotting, protein bands immunoreactive for anti-3beta-HSD were detected at molecular weights of 42 and 37 kDa in both the ventricle and atrium, whereas only a 37 kDa band was recognized in both the aortic arch and abdominal aorta. By immunohistochemistry, immunoreactivity for 3beta,-HSD was detected in both the ventricular and atrial cardiocytes, while immunostaining was also found, though faintly, in the smooth muscles of the aortic arch, abdominal aorta, and inferior vena cava. These results suggest that cardiocytes may synthesize the steroidogenic 3beta,-HSD enzyme.

Animals↗

PubMed1998

Changes of the carotid artery Doppler flow velocity pattern after sublingual nitroglycerin in patients with hypertension.

OBJECTIVE: To evaluate the applicability of carotid Doppler echography for the assessment of changes of peripheral hemodynamics in the hypertensives. SUBJECTS: 28 hypertensives (17 males, 11 females), mean age of 64 yrs and 40 normal controls (24 males, 16 females) mean age of 49 yrs. METHODS: We recorded the right common carotid arterial Doppler flow velocity (BFV) pattern and measured the peak velocities of the percussion wave (P) and late rising tidal wave (T), the ratio of the two (P/T), the time interval between the two peaks corrected by heart rate (P-Tc), systolic flow velocity integral (FVI) and carotid artery diameter (CAD) before and after 0.4 mg dose of subligual nitroglycerin (NTG). RESULTS: 1) In hypertensives, the P wave velocity showed lower and P-Tc interval shorter than those of the normal controls at baseline. 2) After NTG, the P-Tc and P/T increased, but the T and FVI decreased significantly in both groups of subjects. 3) The P/T ratio was less significantly increased after NTG in the hypertensives than in the controls. These results suggest that NTG might have been involved in concomitant reduction and delay of the wave reflection from the peripheral vessels, preferentially in the normal subjects than in hypertensives. CONCLUSIONS: The carotid Doppler echography can be useful for the evaluation of the changes of hemodynamics in the peripheral vessel such as carotid artery in hypertensive subjects.

Administration, Sublingual↗

PubMed1997

Functional differences between Stat3alpha and Stat3beta.

Stat3beta is a short form of Stat3 that differs from the longer form (Stat3alpha) by the replacement of the C-terminal 55 amino acid residues of Stat3alpha by 7 residues specific to Stat3beta. In COS cells transfected with Stat3 expression plasmids, both Stat3alpha and Stat3beta were activated for DNA binding and transcription by the same set of growth factors and cytokines and both, when activated, formed homodimers and heterodimers with Stat1. Only Stat3beta was active in the absence of added cytokine or growth factor. Activation of each form, including constitutive activation of Stat3beta, was correlated with the phosphorylation of tyrosine 705. Activated Stat3beta in transfected COS cells was more stable and had greater DNA-binding activity than activated Stat3alpha. However, relative to DNA-binding activity, Stat3alpha showed greater transcriptional activity than Stat3beta. A mutant of Stat3alpha lacking its highly acidic C-terminal 48 amino acids had properties indistinguishable from Stat3beta. We conclude that Stat3alpha and Stat3beta have significantly different properties due to the presence or absence of the acidic C-terminal tail of Stat3alpha rather than the C-terminal sequence peculiar to Stat3beta. In addition to its effect on transcription, we speculate that the acidic tail may destabilize the active dimeric form of Stat3alpha, resulting in lower DNA-binding activity of the Y705-phosphorylated form compared to Stat3beta and in more rapid dephosphorylation.

Acute-Phase Proteins↗

PubMed1996

In vitro activation of Stat3 by epidermal growth factor receptor kinase.

Stat proteins are SH2 domain-containing transcription factors that are activated in cells by various cytokines and growth factors. In the case of cytokines whose receptors lack protein kinase activity, phosphorylation-activation is mediated by members of the JAK family of tyrosine protein kinases. In the case of growth factors whose receptors have intrinsic tyrosine protein kinase activity, it is thought that Stat proteins can be activated either directly by the receptor or indirectly through JAK proteins. To test the possibility of direct activation, we have used purified Stat3 alpha, Stat3 beta, and epidermal growth factor receptor kinase produced in recombinant baculovirus-infected Sf9 insect cells. The Stat proteins formed a stable complex with the receptor kinase, and they were phosphorylated on tyrosine by the receptor kinase and activated for binding to DNA, properties shared with Stat proteins purified from Sf9 cells coexpressing JAK1 or JAK2. Both JAK-phosphorylated Stat3 beta and Stat3 beta phosphorylated in vitro by the receptor kinase were 20-50 times more active on a molar basis for DNA binding than phosphorylated Stat3 alpha. We conclude that Stat3 isoforms can be directly phosphorylated and thereby activated in vitro by the epidermal growth factor receptor kinase.

Animals↗

PubMed1996

Prolonged intraocular pressure reduction following intravitreal barium injection in rabbits.

The isolated ciliary epithelium contains barium-inhibitable potassium channels. The present study was aimed at testing the in vivo effects of barium on aqueous humor dynamics in rabbits. BaCl2 was administered to one eye by topical delivery or intravitreal injection. Dynamic measurements included intraocular pressure, outflow facility, episcleral venous pressure and aqueous flow (fluorophotometry). Barium dynamics were studied using 133Ba. Intraocular pressure was not altered after topical administration of BaCl2. 133Ba was not detected in the aqueous after delivery of eyedrops containing the radiochemical. Intraocular pressure decreased following intravitreal injection of BaCl2 (0.15 microgram). The onset of this pressure reduction was 12 to 16 hr, the maximum decrease (-11.3 mmHg) occurred at 2 days, and the effect persisted (-4.2 mmHg) for approximately 12 days after the injection. Outflow facility and episcleral venous pressure were not altered. However, aqueous humor flow 5 to 6 days after the injection was decreased by 42% to 63% as determined by fluorophotometry or calculated tonographic data. The injection was not associated with findings of intraocular inflammation. Radioactivity was detected in the vitreous within the first 3 days after the injection; however, activity was present in the ciliary body, equally distributed between the cell membrane and soluble fractions, seven days after the injection. Intravitreally injected BaCl2 results in a prolonged intraocular pressure decrease relating to reduced aqueous formation. While the mechanism(s) for the BaCl2-induced decrease in pressure are not clear, possibilities include a Ba2+ interaction with ciliary epithelial K+ or N-type Ca2+ channels.

Animals↗

PubMed1991

Transient expression of progesterone receptor messenger RNA in ovarian granulosa cells after the preovulatory luteinizing hormone surge.

The ovarian steroid progesterone affects reproductive physiology by regulating the expression of specific genes in target tissues. In an attempt to address the question of whether the ovary itself is a target tissue for progesterone action, we have examined the localization and regulation of progesterone receptor (PR) mRNA in the rat ovary. We used the polymerase chain reaction to clone the steroid-binding domain of the rat PR from uterine cDNA and used this as a probe to isolate a larger cDNA from a rat placental cDNA library. We used RNA filter hybridization, a quantitative reverse transcription-polymerase chain reaction amplification assay, and in situ hybridization to detect PR mRNA in the rat ovary. Expression of the PR gene was initially studied in an immature animal model; 23-day-old rats were treated with either PMSG or PMSG followed by hCG. We found little or no PR mRNA in the ovaries of control or PMSG-treated animals; however, the mRNA was highly expressed in the granulosa cells of large follicles in the ovaries of animals treated with PMSG followed by hCG. Other cell types, including thecal and interstitial cells, did not express detectable levels of PR mRNA. The PR mRNA was induced more than 20-fold in the immature ovary 5 h after hCG administration and was down-regulated to near-basal levels by 12 h after hCG administration. In a subsequent series of experiments, we examined PR gene expression in adult rats during the estrous cycle. The expression of PR mRNA was transient and was tightly coupled to the preovulatory LH surge on proestrous evening. PR mRNA was localized to the granulosa cells of mature ovarian follicles during the estrous cycle. In cycling animals treated with pentobarbital to block the preovulatory LH surge, no induction of PR mRNA on proestrous evening was observed. This transient, hormonally regulated, and cell-specific expression of the PR gene in the rat ovary strongly suggests an important intraovarian function for progesterone during the rat reproductive cycle.

Amino Acid Sequence↗

PubMed1990

Gonadotropin-releasing hormone gene expression during the rat estrous cycle: effects of pentobarbital and ovarian steroids.

Although hypothalamic GnRH release is known to be modulated by neural and hormonal factors, the relationship between altered GnRH secretion and GnRH synthesis remains unclear. In an attempt to address this question, we examined GnRH gene expression in the rat hypothalamus using in situ hybridization histochemistry. An 25S-labeled antisense RNA probe was used to identify neurons expressing GnRH mRNA in an area that included the diagonal band of Broca, the organum vasculosum of the lamina terminalis, and the preoptic area. The number of GnRH mRNA-expressing cells was determined at various times during the rat estrous cycle. During proestrus, the number of GnRH mRNA-expressing cells decreased somewhat at 1400-1600 h, increased significantly at 1800 h (the time of the LH surge), then gradually returned to basal levels at 2200 h. Expression did not change substantially at other times during the estrous cycle. To understand this close temporal relationship between the LH surge and increased GnRH mRNA levels, we examined GnRH gene expression in proestrous animals in which the LH surge was blocked with pentobarbital. Pentobarbital treatment blocked the increase in the number of GnRH mRNA-expressing cells normally observed at 1800 h in saline-treated controls, suggesting that the increase in GnRH gene expression is closely coupled to secretion of GnRH from the hypothalamus. Finally, we addressed the question of whether ovarian steroids have direct effects on GnRH gene expression by examining GnRH mRNA levels in ovariectomized steroid-treated rats at a time before (1100 h) and a time after (1800 h) hypothalamic GnRH hypersecretion. At 1100 h, no significant changes were observed, but at 1800 h, estrogen-treated rats showed a significant increase in both the number of GnRH mRNA-expressing cells and serum LH levels. This suggests that estrogen influences GnRH gene expression indirectly, perhaps by altering hypothalamic GnRH release. Our results in each of these models suggest that GnRH mRNA levels increase in response to GnRH hypersecretion at the time of the LH surge.

Animals↗

PubMed1989

Spontaneous changes in LHRH release during the rat estrous cycle, as measured with repetitive push-pull perfusions of the pituitary gland in the same female rats.

In the present study, we examined the in vivo release profiles of luteinizing hormone-releasing hormone (LHRH) during the rat estrous cycle by utilizing repetitive push-pull perfusions of the anterior pituitary in the same freely behaving animal. Throughout the estrous cycle, LHRH levels were higher than those reported from previous work using a push-pull cannula placed in the mediobasal hypothalamus. A significant increase in LHRH input to the anterior pituitary was obtained in proestrus (Pro), though the magnitude of increment was different among animals. This LHRH increment in Pro was attributable to a significant increase in the amplitude of LHRH pulses. Interestingly, no changes were observed in the frequency of LHRH pulses (about 1 pulse/50 min) throughout the estrous cycle. The data demonstrate that the anterior pituitary of female rats receives an increased amount of LHRH during Pro due to changes in the amplitude of the LHRH signal without changes in the frequency.

Animals↗

PubMed1987

Pregnanolone, a metabolite of progesterone, stimulates LH-RH release: in vitro and in vivo studies.

The effect of 5 beta- and 5 alpha-reduced progestins on luteinizing hormone-releasing hormone (LH-RH) release was examined using either an in vitro superfusion or an in vivo push-pull perfusion (PPP) technique. Ovariectomized rats (at least 6 days post operation: OVX) were implanted subcutaneously in the neck region with a silastic capsule containing 17 beta-estradiol (235 micrograms/ml: E2). Two days afterwards, these OVX + E2 rats were subjected to experimental conditions. Pregnanolone(5 beta-pregnane-3 beta-ol-20-one) at a low concentration of 0.01 ng/ml and an apparent latency of 1 h stimulated in vitro LH-RH release from superfused hypothalamic fragments containing the preoptic-anterior hypothalamic-mediobasal hypothalamic area (POA-AHA-MBH). The stimulatory effect of pregnanolone required estrogen-priming and a pulsatile mode of administration. In addition, the effect appeared quite specific since other closely related steroids such as epipregnanolone, R-5020 and 5 alpha-DHP were ineffective. In OVX + E2 rats bearing a push-pull cannula (PPC) in the hypothalamic area, in vivo infusion of repetitive pulses of pregnanolone through the PPC was also effective, confirming in vivo the stimulatory effect of pregnanolone on LH-RH release obtained from in vitro preparations. In these experiments, the same OVX + E2 rats served both as an experimental animal receiving pulses of pregnanolone and as a control subject when perfused only with medium after a week interval. The basal release rate of LH-RH and the response to pulsatile pregnanolone were variable among animals apparently due to different locations of PPC in the hypothalamus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗