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Biomedical subjects

J C Porter

Publications and source records attributed to J C Porter.

At least 181 records · Page 10Linked to original sources
PubMed1977

Dopamine in hypophysial portal plasma of the rat during the estrous cycle and throughout pregnancy.

Catecholamine levels in hypophysial portal plasma were determined in pregnant and non-pregnant female rats as well as in intact and castrated male rats, using a radioenzymatic assay for the simultaneous determination of dopamine, norepinephrine, and epinephrine in 50 mul of plasma. Portal and arterial blood were collected from anesthetized rats at 7 mul/min for 60 min. During the collection, blood was kept at 0 C, a temperature at which endogenous catecholamines were relatively stable. Dopamine was present in high concentrations in hypophysial portal plasma thorughout pregnancy, attaining a level near 20 ng/ml on the 20th day of gestation. Dopamine levels in arterial plasma from the same rats were low or undetectable (0.4--0.8 ng/ml1. Norepinephrine and epinephrine was undetectable (less than 0.6 ng/ml) in portal as well as arterial plasma from these rats. The major catecholamine in extracts of the hypothalamus from pregnant rats was norepinephrine, whereas that in the posterior pituitary was dopamine. Dopamine levels in portal plasma collected during proestrus, estrus, diestrus 1, and diestrus 2, were 1.32 +/- 0.21 (mean +/- SE), 3.87 +/- 0.96, 3.11 +/- 0.73, and 2.3 +/- 0.45, respectively. Dopamine in portal plasma from intact and from castrated male rats was approximately 0.6 ng/ml. Norepinephrine and epinephrine were not detectable in either portal or arterial plasma from these animals. It is concluded 1) that dopamine is secreted into hypophysial portal blood in significant quantities during pregnancy, 2) that hypothalamic secretion of dopamine in cyclic rats is greatest during the day of estrus and early diestrus and at least on the day of proestrus, and 3) that these findings support the view that dopamine of hypothalamic origin may have an important role in the regulation of anterior pituitary function.

Animals↗
PubMed1977

Release of luteinizing hormone releasing hormone and thyrotropin releasing hormone from a synaptosome-enriched fraction of hypothalamic homogenates.

A mitochondrial fraction prepared from homogenates of rat hypothalamic tissue was found by means of electron microscopy to be enriched with synaptosomes. The release of luteinizing hormone releasing hormone (LHRH) and thyrotropin releasing hormone (TRH) from this preparation was investigated. After incubation, the synaptosomes were re-isolated by ultrafiltration; and the concentration of LHRH and TRH in the ultrafiltrate was determined by radioimmunoassay. When the synaptosome-enriched preparation was incubated in 0.32M sucrose at 1 or 30 C, less than 10% of the total LHRH and TRH was recovered in the ultrafiltrate. The two hormones were released by depolarizing concentrations (60 mM) of K+ in a Ca++-dependent manner, and the stimulatory effect of K+ was essentially complete within 2 min. In the presence of 2 mM Ca++, the release of LHRH and TRH increased with increasing K+ concentrations in the range 30-120 mM. Prostaglandin E2 (PGE2), PGF2 alpha, and PGF2 beta had little if any effect on LHRH or TRH release. When the synaptosome-enriched fraction was incubated in Hanks' balanced salt solution, the release of LHRH and TRH was about 10 times greater than that seen in 0.32M sucrose. It is concluded that a synaptosome-enriched fraction from the hypothalamus contains readily releasable pools of LHRH and TRH which are mobilized rapidly by depolarizing concentrations of K+ in a Ca++-dependent manner.

Animals↗
PubMed1977

Ontogeny of the subcellular compartmentalization of thyrotropin releasing hormone and luteinizing hormone releasing hormone in the rat hypothalamus.

The 900 x g supernatant fluid prepared from hypothalamic homogenates from male and female rats (ranging in age from -1 to 120 days) was fractionated by means of continuous sucrose density gradient centrifugation. Thyrotropin releasing hormone (TRH) and LH releasing hormone (LHRH) in the gradient fractions were quantified by radioimmunoassay. In adult hypothalamic homogenates, TRH and LHRH were associated with two populations of particles distinguishable by their sedimentation properties. Each peptide was in turn distributed in two subpopulations of parties differing in size but similar in density. The distribution of each peptide within its subpopulations of particles was found to be a function of age. In hypothalami of 22-day-old fetuses, TRH was associated almost entirely with the subpopulation of small particles. However, in the neonates, an age-dependent increase in the fractional amount of the TRH confined to the subpopulation of large particles was observed. By the 7th day of age, the peptide was equally distributed in the two subpopulations. The buoyant density of the 1-day-old neonatal particles and that of the adult small and large particles containing TRH was similar. The ontogeny of the subcellular compartmentalization of LHRH differed appreciably from that of TRH. LHRH was barely detectable in hypothalami of 22-day-old neonates. Nevertheless, at this age, the peptide was confined primarily to the subpopulation of large particles, and a similar compartmentalization was noted in hypothalami of 5- and 7-day-old neonates. However, in hypothalami of 14-day-old males and 21-day-old females, association of LHRH with the subpopulation of small particles was evident. It is concluded that 1) the nature of the hypothalamic subcellular compartmentalization of TRH and LHRH is age dependent, 2) the compartmentalization of each peptide in neonatal hypothalami differs from that in the adults, and 3) the development of the mature profile of subcellular compartmentalization of TRH and LHRH proceeds asynchronously.

Aging↗
PubMed1977

Progesterone and 5alpha-pregnane-3,20-dione in peripheral blood of normal young women: Daily measurements throughout the menstrual cycle.

The peripheral plasma concentrations of progesterone and 5alpha-pregnane-3,20-dione were measured daily throughout the ovarian cycle of five presumptively ovulatory women. The concentrations of progesterone and 5alpha-pregnane-3,20-dione during the follicular phase were 0.11 +/- 0.02 ng/ml (mean +/- SE) and 0.16 +/- 0.01 ng/ml, respectively. In four of these women the concentrations of both progesterone and 5alpha-pregnane-3,20-dione began to rise immediately after the luteinizing hormone (LH) peak and reached maximal concentrations five to eight days later (progesterone: 8.6 to 19.9 ng/ml; 5alpha-pregnane-3,20-dione: 1.4 to 2.8 ng/ml). The luteal phases in these women, measured from the day of the LH peak to the onset of the next menses, varied from 13 to 18 days. In the other woman with a late LH surge (day 27 of the cycle) the peak concentrations of progesterone and 5alpha-pregnane-3,20-dione were reached four days after the LH peak (8.9 ng/ml and 0.8 ng/ml, respectively). The luteal phase in this woman was 11 days. From the results of this study, it appears that the concentrations of 5alpha-pregnane-3,20-dione in peripheral blood during the luteal phase are proportional to the availability of progesterone as substrate for the 5alpha-reductase enzyme system.

Female↗
PubMed1977

Metabolism of catechol estrogen by human erythrocytes.

In a study designed to evaluate the kinetics of catechol estrogen formation from plasma estrone in vivo, we obtained evidence that the red blood cell (RBC) enzyme, catechol-O-methyl transferase, catalyzes the transformation of 2-hydroxyestrone to 2-methoxyestrone. Under in vitro conditions, the rate of conversion of 2-hydroxyestrone to 2-methoxyestrone by human RBC's was such that 7 nmol of 2-methoxyestrone were formed per h per ml of RBC.

Catechol O-Methyltransferase↗
PubMed1977

Embryonic testicular regression. A clinical spectrum of XY agonadal individuals.

Aberrations of fetal sexual development were studied in three XY agonadal individuals. Two were phenotypic females with primary amenorrhea, sexual infantilism, and no internal genital structures. Plasma androstenedione and testosterone concentrations were similar to those of prepubertal children and increased after ACTH infusion. The daily production rates of estrone were low. The third agonadal XY individual, a phenotypic male, developed gynecomastia in response to approximately 40 mug of estrone produced daily by the extraglandular aromatization of plasma androstenedione. All plasma testosterone was accounted for by the conversion of plasma androstenedione. The absence of internal genitalia, the prepubertal external genitalia in the phenotypic females, and the incomplete growth of both the internal and external genital structures in the phenotypic male subject suggest that testicular elaboration of müllerian regression substance occurred, but that regression of the testes occurred subsequently during varying stages of embryogenesis. In the females, testicular regression occurred prior to the initiation of fetal testicular production of androgen. On the other hand, in the male subject, testicular activity persisted longer; thus, both müllerian duct regression and embryonic virilization of wolffian ducts and genital tubercles occurred.

Adolescent↗
PubMed1977

The origin of androgen and estrogen in a virilized postmenopausal woman with bilateral benign cystic teratomas.

Clitoromegaly was observed in a 73-year-old woman who had bilateral ovarian benign cystic teratomas that contained only epithelial derivatives. Scattered in the stroma of these ovaries were clusters of hyperplastic cells. The plasma testosterone production rate was 2.4 mg/day, a value that is ten times greater than that of normal postmenopausal women. The elevated plasma concentrations of testosterone and androstenedione decreased to normal by the second day after bilateral oophorectomy. Ovarian venous concentrations of testosterone and androstenedione were also increased and were considerably greater than those in peripheral blood. Estrone production was 68 microng/day, most of which could be accounted fo by the extraglandular formation from androstenedione. Estradiol production was 71 microng/day, of which 75% was computed to arise from extraglandular formation and the remainder likely arose by ovarian secretion. The modest increase in estrogen production was associated with slight cystic hyperplasia of the endometrium. From this study we conclude that the hyperplastic ovarian stroma was the source of the excessive androgen production.

Aged↗
PubMed1976

Inhibition of degradation and measurement of immunoreactive thyrotropin-releasing hormone in rat blood and plasma.

A radioimmunoassay (RIA) for thyrotropin-releasing hormone (TRH) is described. The cross-reactivity of the antiserum was tested with 26 analogs of TRH, 5 amino acids, and LH-releasing hormone. Use of this RIA revealed that inactivation of TRH by rat blood was prevented if the blood was frozen and thawed prior to its incubation with TRH. This procedure did not interfere with the binding of TRH to its antibody. The degradation of TRH by blood or plasma was inhibited by 2,3-dimercaptopropanol (BAL) or benzamidine, but these compounds nonspecifically inhibited the binding of [125I]TRH to anti-TRH. At 37 C, 50% of the synthetic TRH added to rat blood was degraded within seconds, whereas at 1C, 60-65% was recovered after 90 min. When blood was frozen and thawed prior to its incubation with TRH at 1C, essentially all of the hormone was recovered after a 90-min incubation period. In contrast, incubation of TRH with frozen and thawed blood at 37 C resulted in a rapid loss of TRH. BAL (10 mM) or bensamidine (100 mM) afforded complete protection for TRH for at least 30 min at 1 C. At 37 C, protection was incomplete. Exposure of rats to cold (2C) resulted in a significant increase in serum TSH levels, but TRH was undetectable (less than3 pg) in 100 mul of blood regardless of whether the blood contained BAL (10 mM) or benzamidine (100 mM), or was frozen quickly and thawed before RIA. However, when 5-8 ml of trunk blood was extracted with methanol, 8-11 pg/ml of TRH was found, and the TRH levels were slightly but significantly elevated after cold exposure.

Amidines↗
PubMed1976

Prostaglandin-induced release of anterior pituitary hormones: structure-activity relationships.

Prostaglandins (PG's) of the E, F, A, or B series were infused into a lateral ventricle of the brain of adult male rats, and the efficacy of each PG to stimulate the discharge of LH, prolactin, and TSH from the pituitary gland was determined. PGE2, PGF2alpha, and PGF2beta were found to be potent stimulators of LH release. The release was considerably less when PGE1, PGF1beta, PGA2, or PGB2 was infused. The basal release of LH was not altered by infusion of PGF1alpha, PGA1, PGB1, or the control solution. It is suggested that the cis double bond in the 5,6 position and the 11-hydroxyl group are essential for the LH releasing activity of PG's and that these functional groups may be of importance for activation of a receptor at the level of the brain. Prolactin secretion was stimulated 6 to 7-fold by the infusion of 5 mug of PGE2, but 20 mug had no stimulatory effect. PGF2beta caused a 3 to 4-fold increase in basal plasma prolactin concentration and was the only PG tested other than PGE2 that stimulated prolactin release. None of the PG's infused intraventricularly affected TSH secretion.

Animals↗
PubMed1976

A sensitive radioenzymatic assay for dopamine, norepinephrine, and epinephrine in plasma and tissue.

A double-isotope, radioenzymatic assay for measuring dopamine, norepinephrine, and epinephrine in one sample is described. The assay procedure includes incubation, solvent extraction, and thin-layer chromatography. Dopamine, norepinephrine, and epinephrine were incubated with catechol-O-methyl transferase (COMT) and [3H]S-acenosyl methionine ([3H]SAM) and were converted to the O-methylated tritiated derivatives: [3H]methoxytyramine, [3H]normetanephrine, and [3H]metanephrine, respectively. After several extraction steps the O-methylated products were purified by means of two-dimensional, thin-layer chromatography using silica gel. The thin-layer chromatographic system resulted complete separation of the three O-methylated compounds with an overlap of only 1-2%. The assay was linear from 0 to 5 ng for each catecholamine and had a sensitivity of 10-30 pg. The addition of large amounts of plasma reduced the activity of COMT, but increasing the magnesium concentration in the incubation mixture and the addition of EGTA to plasma samples improved the recoveries. Each sample was corrected for losses incurred during extraction and chromatography by using [14C]methoxytyramine, [14C]normetanephrine, and [14Ci1metanephrine that were added at the end of incubation. Several catechol compounds known to be O-methylated by COMT were examined for crossreactivity. Of the substances tested, only dihydroxyphenylalanine (DOPA) exhibited cross-reactivity. However, the apparent 30% cross-reactivity of DOPA with dopamine was due to the presence of decarboxylase activity in the COMT preparation. As little as 50 mul of trunk plasma from decapitated rats was sufficient for the determination of the three catecholamines.

Adrenal Glands↗
PubMed1976

Initiation of human parturition. V. Progesterone binding substance in fetal membranes.

This study was undertaken as part of an investigation of the potential role of progesterone metabolism within fetal membranes in the initiation of human labor. The results of this study provide evidence that a progesterone binding substance is present in amnion and chorion laeve during the last few days of pregnancy. This substance binds progesterone, cortisol, and 5alpha-dihydroprogesterone but does not bind 20alpha-hydroxy-4-pregnen-3-one, R 5020, or dexamethasone. We conclude that this is a previously undescribed progesterone binding substance and propose a possible mechanism by which this substance may be involved in the initiation of human parturition.

17-alpha-Hydroxypregnenolone↗
PubMed1975

The endocrinology of human chorionic gonadotropin-secreting testicular tumors: new methods in diagnosis.

Serum from 59 men with testicular masses was examined for the presence of human chorionic gonadotropin-beta. Results indicate: 1) In patients with testicular tumor human chorionic gonadotropin-beta serves as a sensitive and specific marker of tumor activity with an incidence of 28%. 2) Because human chorionic gonadotropin-beta levels correlate with response to therapy this test will be useful in selecting men for adjunctive irradiation or chemotherapy. 3) Radioimmunoassay for human chorionic gonadotropin-beta is far more sensitive and specific than conventional methods for detecting human chorionic gonadotropin production. 4) After unilateral orchiectomy for carcinoma of the testis elevated serum luteinizing hormone levels are common and may be unrelated to the presence or activity of residual tumor. 5) Human chorionic gonadotropin-beta-producing tumors were associated with increased estradiol and testosterone levels and significantly depressed serum follicle stimulating hormone levels in this series. 6) The prognostic implications of the presence of human chorionic gonadotropin-beta are not yet fully understood. The importance of this study is the fact that men with testicular tumors have a high incidence of human chorionic gonadotropin-beta secretion and this fact provides the physician with a powerful new tool for examining the various aspects of tumor activity. It also shows the feasibility for prospective screening of patients with a wide variety of neoplasms of differing histologic types.

Adolescent↗