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Biomedical subjects

T Song

Publications and source records attributed to T Song.

At least 37 records · Page 2Linked to original sources

Insulin acutely inhibits cultured vascular smooth muscle cell contraction by a nitric oxide synthase-dependent pathway.

Insulin acutely decreases contractile agonist-induced Ca2+ influx and contraction in endothelium-free cultured vascular smooth muscle (VSM) cells, but the mechanism is not known. Since it has been reported that insulin-induced vasodilation in humans is linked to nitric oxide synthase activity, we wished to determine whether insulin inhibits Ca2+ influx and contraction of cultured vascular smooth muscle cells by a nitric oxide synthase-dependent pathway. Primary cultures of endothelial cell-free VSM cells from canine femoral artery were preincubated with and without 1 nmol/L insulin for 30 minutes, and the 5-minute production of cGMP was measured. Insulin alone did not affect cGMP production, but in the presence of 10(-5) mol/L serotonin insulin stimulated cGMP production by 60%. N(G)-monomethyl-L-arginine (0.1 mmol/L), an inhibitor of nitric oxide synthase, inhibited the conversion of arginine to citrulline by these cells, blocked insulin-stimulated cGMP production, and blocked the inhibition by insulin of 5-hydroxytryptamine (5-HT)-stimulated Mn+2 (a Ca2+ surrogate) influx and contraction. Insulin did not affect contraction of VSM cells grown under conditions designed to deplete the cells of tetrahydrobiopterin, an essential cofactor of nitric oxide synthase. These studies demonstrate that insulin acutely inhibits 5-HT-stimulated Ca2+ influx and contraction of endothelium-free cultured VSM cells by a nitric oxide synthase-dependent mechanism.

Animals↗

Effect of folding on the export of ribose-binding protein studied with the genetically isolated suppressors for the signal sequence mutation.

Ribose-binding protein (RBP) has a bilobate structure and functions in the periplasm of Escherichia coli. Mutations that affect the folding of RBP were isolated as intragenic suppressors for the export-defective signal sequence mutation. Of 13 different mutational changes found in the mature region, 12 were located in the several peptides forming the N-domain, and one in the C-domain. Translocation kinetics of mutant proteins were analyzed by pulse-labeling and chase experiments, showing the recovery of precursor processing in the range of 42 to 70%. Folding properties of seven mutant RBPs purified were investigated in vitro by means of tyrosine fluorescence. The stability of the mutant proteins, estimated by equilibrium analysis in the presence of denaturant, were reduced by 2.1 to 5.1 kcal/mol of changes in free energy of unfolding. All the mutant proteins showed retardation in folding rate by 4.4 to 63-fold compared to wild-type while unfolding was little affected. The only exception was the L129Q that has a change in the C-domain resulting in unstability due to faster unfolding. Our approach took advantage of an involvement of the folding process in protein export, which was genetically employed to dissect the folding pathway of RBP. As a result, amino acid residues that are specifically involved in the folding pathway of RBP were identified. Most of them are concentrated in one of the subdomains, suggesting that the folding event in the N-domain of RBP is crucial in the rate-determining step.

Calorimetry↗

Insulin-stimulated glucose transport inhibits Ca2+ influx and contraction in vascular smooth muscle.

BACKGROUND: Insulin attenuates serotonin-induced Ca2+ influx, the intracellular Ca2+ transient, and contraction of cultured vascular smooth muscle cells from dog femoral artery. These studies were designed to test whether insulin-induced glucose transport was an early event leading to the inhibitory effects of insulin on Ca2+ influx, intracellular Ca2+ concentration, and contraction in these cells. METHODS AND RESULTS: Insulin 1 nmol/L stimulated the 30-minute uptake of [3H]2-deoxyglucose in these cells via a phloridzin-inhibitable mechanism. Contraction of individual cells was measured by photomicroscopy, intracellular Ca2+ concentration was monitored by measuring fura 2 fluorescence by use of Ca(2+)-sensitive excitation wavelengths, and Ca2+ influx was estimated by the rate of Mn2+ quenching of intracellular fura 2 fluorescence when excited at a Ca(2+)-insensitive wave-length. In the presence of 5 mmol/L glucose, preincubation of cells for 30 minutes with 1 nmol/L insulin inhibited 10(-5) mol/L serotonin-induced contraction of individual cells by 62% (P < .01) and decreased the serotonin-stimulated component of Mn2+ influx by 78% (P < .05). Removing glucose from the preincubation medium or adding 1 mmol/L phloridzin completely eliminated these effects of insulin. Insulin lowered the serotonin-induced intracellular Ca2+ peak by 37% (P < .05), and phloridzin blocked this effect of insulin. When glucose uptake was increased to the insulin-stimulated level by preincubation of the cells for 30 minutes with 25 mmol/L glucose in the absence of insulin, serotonin failed to stimulate Mn2+ influx, the serotonin-induced Ca2+ peak was decreased by 46% (P < .05), serotonin-induced contraction was inhibited by 60% (P < .01), and addition of insulin did not further inhibit contraction. CONCLUSIONS: Since the effects of insulin on serotonin-stimulated Ca2+ transport, intracellular Ca2+ concentration, and contraction were dependent on glucose transport and were duplicated when glucose transport was stimulated by high extracellular glucose concentration rather than insulin per se, it is concluded that insulin-stimulated glucose transport is an early event that leads to decreased Ca2+ influx and contraction in vascular smooth muscle.

Animals↗

Synthesis and structure-activity relationships of stilbene retinoid analogs substituted with heteroaromatic carboxylic acids.

Retinoids elicit biological responses by activating a series of nuclear receptors. Six retinoid receptors belonging to two families are currently known: retinoic acid receptors (RAR alpha,beta,and gamma) and retinoid X receptors (RXR alpha,beta,and gamma). Stilbene retinoid analogs of retinoic acid (RA), such as (E)-4-[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)prope n-1- yl]benzoic acid (TTNPB, 1) and (E)-4-[2-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2-naphthalenyl)pro pen-1- yl]benzoic acid (3-methyl-TTNPB, 2), display differential RAR and RXR activities, depending on the substituent at C3 of the naphthalene ring. We report here structural modifications of the benzoate moiety of 2 that result in analogs with greater RXR selectivity as well as those with pan-agonist (activate both RAR and RXR receptors) activities, analyze the structural features that impart receptor selectivity, and describe a stereoselective method for the synthesis of these analogs. The biological activities associated with the RAR and RXR receptors were examined by testing representative examples with different receptor activation profiles for their ability to induce tissue transglutaminase (Tgase) activity in a human promyelocytic leukemia cell line (HL-60 cdm-1) and to inhibit tumor-promoter-induced ornithine decarboxylase (ODC) activity in hairless mouse skin. These results suggest that RAR agonists and RXR agonists may have different therapeutic applications. Finally, we show that RXR agonists are significantly reduced in teratogenic potency relative to RAR agonists and may therefore have significant advantages in clinical practice.

Abnormalities, Drug-Induced↗

Insulin inhibits dog vascular smooth muscle contraction and lowers Ca2+i by inhibiting Ca2+ influx.

Essential hypertension, obesity and non-insulin-dependent diabetes are associated with resistance to insulin-induced glucose disposal. Because physiological concentrations of insulin inhibit vascular smooth muscle (VSM) contraction in vivo, it has been proposed that resistance to insulin-induced inhibition of VSM contraction might be partly responsible for the elevated vascular resistance found in these clinical conditions. Nevertheless, it is not known how insulin inhibits contraction of normal VSM. Several workers have demonstrated that insulin attenuates the agonist-induced intracellular Ca2+ (Ca2+i) transient in VSM, although the identity of the sarcolemmal and/or sarcoplasmic reticular Ca2+ transport systems that are affected by insulin is controversial. Our laboratory has examined the effects of a physiological concentration of insulin on contraction and Ca2+ transport in cultured VSM cells from canine femoral artery. We have found that insulin inhibits agonist-induced contraction and attenuates the agonist-induced Ca2+i transient by inhibiting Ca2+ influx, but not by increasing Ca2+ efflux or inhibiting Ca2+ release from internal stores. Insulin also stimulates ouabain-sensitive 86Rb+ uptake (Na(+)-K+ pump activity) and does not inhibit VSM contraction in the presence of ouabain. Our data support the hypothesis that insulin stimulates Na(+)-K+ pump activity, resulting in hyperpolarization of the cell and decreased Ca2+ influx via voltage-operated channels.

Animals↗

Insulin inhibits serotonin-induced Ca2+ influx in vascular smooth muscle.

BACKGROUND: Insulin in physiological concentrations attenuates the agonist-induced intracellular Ca2+ ([Ca2+]i) transient and inhibits contraction in individual nonproliferated cultured canine femoral artery vascular smooth muscle cells (VSMCs). In the present study, we wished to define the effects of insulin on individual components of Ca2+ transport in vascular smooth muscle. METHODS AND RESULTS: Insulin (40 microU/mL) attenuated the 5-hydroxytryptamine (5-HT, serotonin; 10(-5) mol/L)-induced [Ca2+]i transient (measured by fura 2 fluorescence) in primary confluent canine femoral artery VSMCs in the presence of extracellular Ca2+. In Ca(2+)-free media, the 5-HT-induced [Ca2+]i transient was reduced by 42% and was not affected by insulin. This finding suggested that insulin inhibits 5-HT-induced Ca2+ influx but does not affect sarcolemmal Ca2+ efflux or Ca2+ release from intracellular stores. In support of those conclusions, we found that insulin inhibited the 5-HT-induced component of Mn2+ (a Ca2+ surrogate) influx (measured by fura 2 fluorescence quenching at the Ca2+ isosbestic excitation wavelength). In addition, 5-HT stimulated the rates of 45Ca2+ efflux from intact cells (a measure of sarcolemmal Ca2+ efflux) and from saponin-permeabilized cells (a measure of Ca2+ release from intracellular stores), but insulin did not affect these rates of 45Ca2+ efflux. CONCLUSIONS: We conclude that a physiological insulin concentration attenuates the 5-HT-induced [Ca2+]i transient in confluent primary cultured canine femoral artery VSMCs by inhibiting the 5-HT-induced component of Ca2+ influx but not by affecting sarcolemmal Ca2+ efflux or Ca2+ release from intracellular stores.

Animals↗

Insulin reduces contraction and intracellular calcium concentration in vascular smooth muscle.

Resistance to insulin-induced glucose disposal is associated with hypertension, in accord with recent reports that insulin-induced vasodilation is impaired in men with resistance to insulin-induced glucose disposal. Nevertheless, the mechanism of insulin-induced vasodilation is not known. We wished to determine whether a physiological concentration of insulin inhibits agonist-induced contraction at the level of the individual vascular smooth muscle cell, and if so, how. Dispersed vascular smooth muscle cells from dog femoral artery were grown on collagen gels for 4 to 8 days. Contraction and intracellular Ca2+ concentration of individual cells were measured by photomicroscopy and fura 2 epifluorescence microscopy, respectively. Serotonin and angiotensin II contracted cells in a dose-dependent manner. Preincubation of cells for 20 minutes (short-term) or 7 days (long-term) with insulin (40 microU/mL) inhibited serotonin- and angiotensin II-induced contractions by approximately 50%. Insulin (10 microU/mL) acutely inhibited serotonin-induced contraction by 34%. The maximal effect of high extracellular K(+)-induced contraction was not affected by short-term insulin exposure, but the ED50 for extracellular K(+)-induced contraction was increased from 7.6 +/- 2.5 to 16.0 +/- 3.9 mmol/L (P < .05). Short-term insulin exposure also attenuated the peak rise of the serotonin-induced intracellular Ca2+ transient and increased the rate constant for intracellular Ca2+ decline. Verapamil and ouabain completely blocked the attenuation of agonist-induced contraction by short-term insulin exposure, indicating the importance of voltage-operated Ca2+ channels and the Na(+)-K+ pump for this effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

[Effect of electro-acupuncture at neiguan P6 on sino-atrial conduction in patients without sick sinus syndrome].

The effects of electro-acupuncture (EA) at Neiguan P6 served as a main point and Jianshi P5 as an adjunct point on sino-atrial conduction were studied in 10 patients with normal sinus nodal function. The results were as follows: During EA and in period of intrinsic heart rate (IHR0) the sinoatrial conduction times (SACT) from sinus node electrogram were significantly shortened than that in control, (P < 0.01 and P < 0.001, respectively). But the SACT could not be further shortened by stimulating the acupoints during IHR0 (P < 0.05). It is suggested that EA at Neiguan P6 as a main point could improve sino-atrial conductivity in most patients with normal sinus node function, which seems to be mediated by autonomic nerve system. The normal value of SACT after autonomic nerve blockade needs to be established.

Acupuncture Points↗

[Study on quality of diagnosis in patients with sputum negative pulmonary tuberculosis in rural area].

1194 cases (3.9%) were randomly selected from all newly registered patients with sputum negative pulmonary tuberculosis (PTB) of Jiangsu Province in 1991. After reevaluation by specialists, final diagnosis was made. 94 cases (7.9%) were excluded because of insufficient information, the diagnosis of PTB for 107 patients (9.7%) of the remained 1100 cases were not correct. Results indicate that one of the causes for the low sputum positive rate of newly registered patients with PTB was probably due to the comparatively large proportion of misdiagnosed sputum negative patients.

Adolescent↗

Mutations that affect the folding of ribose-binding protein selected as suppressors of a defect in export in Escherichia coli.

It has been proposed (Randall, L. L., and Hardy, S. J. S. (1986) Cell 46, 921-928) that export of protein involves a kinetic partitioning between the pathway that leads to productive export and the pathway that leads to the folding of polypeptides into a stable conformation that is incompatible with export. As predicted from this model, a decrease in the rate of export of maltose-binding protein to the periplasmic space in Escherichia coli resulting from a defect in the leader sequence was able to be partially overcome by a mutation that slowed the folding of the precursor, thereby increasing the time in which the polypeptide was competent for export. (Liu, G., Topping, T. B., Cover, W. H., and Randall, L. L. (1988) J. Biol. Chem. 263, 14790-14793). Here we describe mutations of the gene encoding ribose-binding protein that were selected as suppressors of a defect in export of that protein and that alter the folding pathway. We propose that selection of such suppressors may provide a general method to obtain mutations that affect the folding properties of any protein that can be expressed and exported in E. coli.

Biological Transport↗

Effects of dynamic fixation on shear behaviour of porcine xenograft valves.

To evaluate an alternative valve fixation technique, we measured the ability of glutaraldehyde-fixed valve tissue to undergo internal shearing during bending. Porcine aortic valves were fixed statically using conventional means, and dynamically while opening and closing repeatedly in a pulse tank. Using a polarized light microscopy technique developed previously, we measured shear deformation angles in thin sections of bent leaflet tissue and calculated shear strains. Statically-fixed leaflet tissue sheared only 1.2% +/- 2.29% (Mean +/- SD) when bent to curvatures of 2.0 mm-1, while dynamically-fixed tissue sheared 5.1% +/- 2.63% (significant at P less than 0.05). It is likely that dynamic fixation increases the ability of prosthetic valve leaflets to shear during bending by reducing the number of interfibre cross-links that would otherwise impede such deformations. Because shear strains reduce internal fibre strains and protect the leaflets against fatigue, prosthetic valves constructed from dynamically fixed tissue should experience lower stresses and hence last longer.

Biomechanical Phenomena↗

Tissue buckling as a mechanism of bioprosthetic valve failure.

Current reports indicate that collagen fiber disruption resulting from cyclic leaflet bending is a factor determining long-term durability of bioprosthetic heart valves. Examination of the opening characteristics of porcine xenografts has shown two areas of high bending curvature that correlate well with sites of leaflet tearing. These are at the free edge and near the attachment of the leaflets to the aortic root. To determine the potential effects of sharp bends in leaflet material, we examined 15 strips each of fresh and glutaraldehyde-treated porcine aortic valve tissue. Leaflet strips were bent to curvatures of 0.18 mm-1 to 6.67 mm-1, histologically processed, sectioned, and examined under a light microscope. We observed severe compressive buckling in the samples taken from bioprosthetic valves but little in the fresh-tissue samples. At physiological curvatures (less than 0.28 mm-1), no buckling occurred in the fresh tissue; at high bending curvatures (2.0 mm-1), the depth of buckling observed in the treated tissue was 100% greater than that in the fresh. We believe that porcine xenograft failure is related to compressive buckling of the aldehyde-treated tissue and is mediated by the systematic breaking of collagen fibers at the site of buckling. We suggest that alternative valve designs and preservation techniques be employed to prevent such abnormal leaflet deformations.

Animals↗

The gonadotropin-releasing hormone containing ventral hypothalamic tract in the fetal rhesus monkey (Macaca mulatta).

A well-defined, gonadotropin-releasing hormone (GnRH)-containing fiber pathway, the ventral hypothalamic tract (VHT), is described by immunostaining in fetal rhesus macaques (109-156 days gestation). The VHT arises above the lateral aspects of the optic chiasm near the supraoptic nucleus, and courses ventromedially close to the ventral hypothalamic surface to terminate in the infundibulum and zona externa of the median eminence. It is formed by the confluence of GnRH-immunopositive (GnRH+) axons from local neurons, from a few GnRH+ cells in the inferior thalamic peduncle, and probably from more anterior neurons in the septum and preoptic area. Bipolar GnRH+ neurons contributing directly to the VHT are grouped at its origin dorsolateral to the optic chiasm, dorsal and medial to the optic tracts, at the infundibular lip, and within the pathway between. At the infundibular lip, GnRH+ perikarya are generally lateral or ventral to the infundibular (arcuate) nucleus, and are rarely within the nucleus itself. Cell bodies here are sometimes tripolar, but GnRH+ intercellular contacts are seldom seen. A few VHT fibers extend to the ventral surface of the brain just beneath the pia mater. Abundant capillaries in the subarachnoid space suggest a possible route for delivery of GnRH to the adenohypophysis in early gestation, before maturation of the hypophysial portal system occurs. Posterior to the infundibulum, a few VHT fibers are joined by descending periventricular fibers forming a dense fiber band beneath the premammillary recess of the third ventricle. Totals of GnRH+ cell bodies in the prosencephalon of the fetal rhesus macaque are estimated to be 5,600 in females (n = 2) and 2,600 in males (n = 3). More than 60% of VHT neurons are located in the medial basal hypothalamus, and the majority of basal hypothalamic GnRH+ neurons (86%) are associated with the VHT. Furthermore, reports of the autonomy of the medial basal hypothalamic-hypophysial unit in control of gonadotropin secretion suggest that the VHT may be the most important GnRH system involved in primate reproduction. It is clear that fetal material may offer the best model to study the GnRH neuronal system in primates.

Animals↗

Immunostaining reveals accumulation of serotonin and coexistence with tyrosine hydroxylase in hypothalamic neurons of acutely stalk-sectioned baboons.

The distribution of serotonin (5-HT) and tyrosine hydroxylase (TH) was examined in the hypothalamus of juvenile baboons, 24 h after infundibular stalk section. Simultaneous immunostaining for 5-HT with peroxidase-antiperoxidase (PAP) and TH with 15 nm colloidal gold (IGS) was performed on Vibratome sections from 3 operated and 1 control female. Light microscopy revealed fine 5-HT immunopositive (5-HT+) fibers, presumably axons, in the suprachiasmatic nuclei and ventromedial hypothalamus (VMH) after stalk section. In addition, focal accumulations of swollen and heavily stained 5-HT+ fibers occurred on the side of the surgical approach. Enlarged fibers were densest in the medial preoptic area, lateral and VMH areas, and the median eminence. TH immunoreactivity (TH+) in VMH cell bodies and axons was only slightly increased over that in controls. Electron microscopy of areas of 5-HT+ and TH+ overlap (medial VMH and adjacent periventricular zone) showed that 5-HT+ profiles were mostly unmyelinated axons and irregular varicosities. A few myelinated 5-HT+ axons were also observed. TH+ perikarya, dendrites, axons and terminals showed gold labeling characteristic for this enzyme. However, colocalization of 5-HT (PAP) and TH (IGS) was present in a number of fiber varicosities in experimental animals only. Both single- and double-labeled profiles occurred in individual thin sections, thus arguing against antibody cross-reactivity. These results indicate that: hypothalamic 5-HT+ fibers project to the median eminence in primates; 5-HT fibers become more obvious after stalk section due to accumulation of transmitter; focal 5-HT+ immunoreactivity in the hypothalamus can increase dramatically after distant and mild surgical trauma, and coexistence of 5-HT and TH in single neurons can appear after acute stalk section and/or trauma in experimental animals. These findings might represent uptake of exogenous 5-HT or amplified expression of endogenous neurotransmitter, suggesting that plasticity of transmitter phenotype might follow acute surgical and/or endocrine intervention in mature primate brain. Neuroendocrine studies employing the stalk-sectioned primate might thus be radically affected.

Animals↗

MR staging of primary colorectal carcinoma: comparison with surgical and histopathologic findings.

BACKGROUND: We retrospectively evaluated the accuracy of magnetic resonance (MR) imaging in staging colorectal cancer and assessing local tumor extent, nodal involvement, and distant abdominal and pelvic metastases. METHODS: Forty-eight patients with primary colorectal carcinoma were referred for presurgical abdominal and pelvic MR imaging. MR imaging included T1-weighted, fat-suppressed T2-weighted, and fat-suppressed gadolinium-enhanced spin gradient-echo imaging. The prospective interpretations of the MR examinations were reviewed. MR depiction of local tumor extent, nodal involvement, and distant metastases at 18 anatomic locations was noted and compared with subsequent surgical and histopathologic findings. RESULTS: Overall TNM MR staging agreed with surgical and pathologic staging in 41 (85%) of 48 patients, including 21 (78%) of 27 colon cancers and 20 (95%) of 21 rectal cancers. For depth of tumor penetration, which was evaluable in 44 patients, MR imaging agreed with pathologic results in 38 (86%) of 44 patients, including 22 (88%) of 25 colon cancers and 16 (84%) of 19 rectal cancers. In 42 (95%) of 44 patients, MR images correctly distinguished tumor confined to the bowel wall (T0, T1, and T2) from tumor with transmural tumor extension (T3 and T4). Regional nodal metastases were depicted in 15 of 22 patients (sensitivity, 68%; accuracy, 83%). Nodal metastases were better depicted for rectal cancer in eight of nine patients, compared with colon cancer in seven of 13 patients. Distant metastases were correctly depicted on MR imaging in 13 of 14 patients (sensitivity, 93%; accuracy, 98%). In the site-by-site analysis, MR imaging prospectively depicted 66 of 77 sites of surgically confirmed metastatic tumor in the abdomen and pelvis (sensitivity, 86%; specificity, 99%; accuracy, 98%). CONCLUSION: MR imaging using currently available techniques can effectively image local tumor extent and distant metastases in patients with colorectal carcinoma. Especially for colon cancer, incomplete depiction of nodal metastases in normal-size lymph nodes remains a limitation of cross-sectional imaging studies.

Aged↗

GnRH-prohormone-containing neurons in the primate brain: immunostaining for the GnRH-associated peptide.

The structure of the prohormone for mammalian gonadotropin releasing hormone (proGnRH) includes the GnRH decapeptide followed by a 56 amino acid GnRH-associated peptide (GAP). In this study, we compared immunostaining of brain neurons and fibers for GAP and GnRH in fetal rhesus monkeys and juvenile baboons. We used antisera against different portions of human and rat GAP (proGnRH 14-24, proGnRH 40-53, and proGnRH 52-66) or against GnRH and the PAP technique. Liquid phase absorption with GAP or GnRH confirmed the specificity of these antisera. Major accumulations of GAP immunoreactive (GAP+) perikarya occurred in the medial septal and preoptic areas and the nucleus of the diagonal band of Broca (44.6% in rhesus, 49.6% in baboon), supraoptic region including the area dorsal to the optic tract (21.9% in rhesus, 23.0% in baboon), and the medial basal hypothalamus (15.7% in rhesus, 16.4% in baboon), especially at the infundibular lip. Occasional cell bodies were scattered throughout the hypothalamic and forebrain regions studied. GAP+ fibers were widely distributed, but formed well-defined pathways such as the periventricular and ventral hypothalamic tract. In addition, GAP+ nerve terminals with various densities occurred in the lamina terminalis, the zona externa of the infundibulum, and behind the infundibular stalk. Fetal rhesus macaques had more GAP+ cell bodies, denser fiber networks, and more distinct pathways than juvenile baboons. However, fiber and terminal immunostaining was somewhat less intense for GAP than GnRH in comparable regions. These results indicate that proGnRH (GAP) is present in the same population of neurons as GnRH in the primate brain. They also suggest that post-translational products of proGnRH are present in perikarya, axons and terminals, and that GnRH and GAP and/or further cleavage products are consecreted into hypophysial portal blood in the primate.

Animals↗