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K J Ryan

Publications and source records attributed to K J Ryan.

At least 145 records · Page 8Linked to original sources
PubMed1979

Progesterone receptor in the hypothalamic cytosol of female rats.

A progesterone (P)-binding component with a sedimentation coefficient of 8S has been demonstrated in hypothalamic cytosol from ovariectomized, estrogen-primed rats using both [H]P-containing sucrose-glycerol gradient analysis and dextran-coated charcoal adsorption of the preisolated 8S component. The association rate constant (K+1) was determined to be 1.90 +/- 0.38 (SD) X 10(6) M-1 min-1 at 0-2 C. The dissociation rate constant (K-1) was 1.86 x 10(-2) min-1, as calculated from the half-dissociation time [37.0 +/- 7.3 (SD) min]. The apparent dissociation constant (Kd) at 0-2 C was determined to be 6-10 nM by Scatchard plot analysis of data obtained from either direct [3HA]P binding or competition of the [3H]P binding by nonradioactive P and by calculating from K-1/K+1. The 8S binding component was protein in nature, and the concentration of binding sites was 12 fmol/mg cytosol protein. On a per U cytosol protein basis, the relative capacities of the specific 8S binding components were: uterus greater than pituitary greater than hypothalamus greater than hippocampus/amygdala greater than cerebral cortex. Competition studies showed a high specificity for P and 5 alpha-dihydroprogesterone. Corticosterone (C), although competing for the binding, had an affinity 8-fold less than P. Implantation of C in adrenalectomized, ovariectomized, estrogen-implanted rats suppressed the 8S binding of [3H]C without affecting the [3H]P binding. The binding of [3H]P to the cytoplasmic 8S component of hypothalamus was greater than that of combined hippocampus and amygdala, while the reverse was observed for the binding of [3H]dexamethasone. These results demonstrate in rat hypothalamic cytosol a tissue and hormone-specific, high affinity, 8S progesterone-binding protein which has many of the properties expected of a hormone receptor.

Animals↗
PubMed1979

The production of progesterone, androgens, and estrogens by granulosa cells, thecal tissue, and stromal tissue from human ovaries in vitro.

The concentrations of steroids in antral fluid, the number of granulosa cells, the status of the oocyte, and the diameter of each follicle were determined in human ovaries so that follicles at each stage of the menstrual cycle could be classified as large (greater than or equal to 8 mm diameter) or small (less than 8 mm diameter) and healthy or atretic. The granulosa cells and thecal-enriched tissue from each follicle and the stromal tissue from each ovary were cultured for 6 days in vitro. The amounts of progesterone (P), androstenedione (delta 4), testosterone, dihydrotestosterone, estrone, and estradiol (E2) generated by the different tissues were measured on days 0, 2, 4, and 6 of culture. It was found that granulosa cells, thecal tissue, and stromal tissue all have the biosynthetic capacity to produce P, delta 4, testosterone, dihydrotestosterone, estrone, and E2. No individual steroid-secreting compartment of the ovaries studied, whether part of the follicle or of the stroma, had the exclusive capability of producing any of the above-named steroids at any stage of the menstrual cycle or at any stage of antral follicle growth or atresia. Although the steroids produced by the human follicle appear not to be unique to any one cell type, the patterns of steroidogenesis by the granulosa and thecal compartments differ from one another and from the stroma throughout follicular maturation and atresia. During follicular development, granulosa cells produce large amounts of E2 and small amounts of delta 4. During the preovulatory phase, cells from large follicles (greater than or equal to 8 mm diameter) differentiate from an estrogen-secreting state into a P- and, to a lesser extent, an delta 4-secreting one. By contrast, during follicular atresia, granulosa cells continue to synthesize delta 4, but their capacity to synthesize estrogen is substantially reduced. Furthermore, granulosa cells from atretic follicles are incapable of transforming from an androgen-secreting state into a P-secreting one in tissue culture. During follicular growth, thecal tissue secretes about 2--3 times more delta 4 than E2. By contrast, during follicular atresia, thecal tissue retains its capacity to synthesize delta 4 but loses much of its capacity to synthesize E2. The in vitro capacity of thecal tissue to produce steroids exceeds that of the stroma (on a per weight basis) from 2- to 500-fold. Thecal tissue from healthy but not from atretic follicles is capable of differentiating from an androgen- and estrogen-secreting state to a predominantly P-secreting one in tissue culture. It is postulated that although steroid synthesis may not be rigidly compartmentalized during follicular development, appreciable amounts of the steroids secreted by the granulosa and theca may enter different compartments before leaving the ovary...

Adult↗
PubMed1979

Hormonally induced tumors of the reproductive system of parabiosed male rats.

Parabiosis of intact male rats to castrated males or oophorectomized females for a period of approximately 20 months resulted in three interstitial cell tumors of the testis. When unilateral nephrectomy was added to the parabiotic procedure in ten pairs, eight interstitial cell tumors of the testis and four adenocarcinomas of the prostate occurred in the target male parabionts. These changes were preceded by elevations in luteinizing and follicle-stimulating hormone levels in the serum of the castrates and high levels of testosterone and, to a lesser degree, of androstenedion in the target partners developing the tumors.

Adenocarcinoma↗
PubMed1978

Plasma prostaglandin metabolites in human labor.

To elucidate the role of prostaglandins in initiating uterine contractions we studied the concentrations of 13,14-dihydro-15-keto-PGE2 (PGE2-M) and 13,14-dihydro-15-keto-PGF2alpha (PGF2alpha-M) in peripheral plasma of pregnant patients. The concentrations of PGE2-M and PGF2alpha-M in pregnant patients at term not in labor were not significantly different from those at midpregnancy. Induction of labor at term pregnancy caused a significant rise of both PGE2-M and PGF2alpha-M. During spontaneous labor there were no significant minute-to-minute fluctuations of plasma PGE2-M and PGF2alpha-M and their concentrations were not different from those at oxytocin-induced labor. Initiation of uterine contractions and abortion at midpregnancy by the intra-amniotic infusion of hypertonic saline was not associated with any change in PGE2-M concentration and a rise in PGF2alpha-M was noted in only one of five patients. The vaginal administration of PGE2 and the intra-amniotic infusion of PGF2alpha were associated in each case with a significant rise of both prostaglandin metabolites. It is concluded that the rise of prostaglandin metabolites in peripheral plasma is secondary to the initiation of uterine contractions at term pregnancy. Such a rise is not usually observed after the initiation of uterine contractions by hypertonic saline at midpregnancy.

Abortion, Induced↗
PubMed1978

Properties of the aromatase system associated with the mitochondrial fraction of human placenta.

The aromatase system associated with the mitochondrial fraction of human term placenta, present at 35--50% the specific activity of the microsomal enzyme, is substantially the same as the microsomal enzyme as determined by the following: 1) The rate of aromatization of androstenedione, 19-nortestosterone, and 16alpha-hydroxytestosterone in mitochondria was a nearly constant proportion of the microsomal rate; 2) Sensitivity to carbon monoxide was the same; 3) The magnitude of cytochrome P-450 Type I spectral interactions with androgen substrates was a constant proportion in mitochondria and microsomes; 4) Sensitivity to an antibody raised against hepatic microsomal NADPH-cytochrome c reductase was the same. When inner and outer mitochondrial membrane subfractions were prepared, the predominant aromatase activity was associated with the outer membrane preparation. This aromatase activity could not be accounted for by microsomal contamination as determined by inosine diphosphatase activity, a microsomal marker. After correction, the rate of aromatization in the outer membrane preparation was almost six times that in the inner membranes and three times that of the whole mitochondrial fraction.

Androstenedione↗
PubMed1978

Estrogen 2-hydroxylase: activity in rat tissues.

Incubation parameters for a radioderivative assay for estrogen 2-hydroxylase have been examined. The assay was found to be specific and sensitive if a chromatographically purified preparation of COMT was used. Estradiol was found to be a better substrate for the 2-hydroxylase than estrone or estriol. The liver had significantly higher estrogen 2-hydroxylase activity than any other tissue examined. The estrogen 2-hydroxylase was highly localized in the microsomal fraction in both the liver and the brain. The male rat was found to have significantly more estrogen 2-hydroxylase activity in the liver than the female rat. In addition, in the male rat liver, the estrogen 2-hydroxylase activity was reversibly inducible by testosterone and was not affected by phenobarbital. In the male and female rat brain the estrogen 2-hydroxylase activities were similar.

Animals↗
PubMed1978

The relationship between frequency of ventilator circuit changes and infectious hazard.

The relationship between frequency of ventilator circuit changes and risk of ventilator-associated pneumonia was studied using 2 independent approaches. The first was an in-use aerosol contamination study with patients on 8-hour, 16-hour, or 24-hour ventilator changing schedules. The second approach was a study comparing the incidence of pneumonia in patients on ventilators for 2 one-year periods when the ventilator circuit changing time differed. In-use aerosol sampling of 513 ventilator treatment periods showed bacterial contamination greater than 100 organisms per aerosol in 1.8 per cent of 8-hour cycles, in 2.5 per cent of 16-hour cycles, and in 5.4 per cent of 24-hour cycles. These differences were not significant. The incidence of ventilator-associated pneumonia was the same for one-year periods when ventilator circuits were changed either every 8 or every 24 hours. It was concluded that changing ventilator circuits every 24 hours provides adequate protection from ventilator-associated pneumonia.

Bacterial Infections↗
PubMed1978

Phylogenetic distribution of aromatase and other androgen-converting enzymes in the central nervous system.

Metabolism of [3H]androstenedione was studied in brain tissue homogenates of opossum, bird, snake, sea turtle, urodele amphibian, teleost, shark, skate, hagfish, and lobster. Estrone, 17 beta-estradiol, or 17 alpha-estradiol was formed by central neural tissues of all species, with the exception of the opossum, hagfish, and lobster. Aromatase activity was concentrated in the forebrain, although some estrogen was synthesized by mid- or hindbrain homogenates of two lower vertebrates (teleost and skate) and the newly hatched chick. 5 alpha-Androstanedione (5 alpha-androstane-3,17-dione) or 5 alpha-dihydrotestosterone were products of metabolism in several nonmammalian vertebrates and in the invertebrate central nervous system also. 5 alpha-Reductase was found in all major brain divisions. These and previously reported comparative studies indicate that the ability to aromatize and otherwise transform androgen substrates is a primitive characteristic of the brain that has been widely conserved phylogenetically.

Androstenedione↗
PubMed1978

Cyclic AMP and cyclic GMP accumulation in hamster pre-ovulatory follicles stimulated with LH and FSH.

Cyclic AMP and cyclic GMP accumulation in hamster pre-ovulatory follicles was determined after in vitro stimulation by LH and FSH. Combined time course and dose response experiments determined that the acute response of the follicles (0-30 min) to LH and FSH was similar with respect to cyclic AMP accumulation. The pattern of cyclic GMP accumulation was, however, distinctly different in LH and FSH stimulated follicles. LH increased follicular cyclic GMP only at the lowest dose (0.005 IU/ml), while higher doses of LH had no effect. In contrast, FSH at all doses stimulated cyclic GMP accumulation. The different cyclic AMP to cyclic relationships generated in the follicles by LH and FSH may be determinants in specificity of hormone action in pre-ovulatory follicles.

Animals↗
PubMed1978

Cyclic AMP and cyclic GMP accumulation by isolated hamster granulosa cells stimulated by LH and FSH.

Cyclic AMP and cyclic GMP accumulation in hamster granulosa cells as a function of gonadotrophin dose (LH or FSH) and time (0-30 min) was determined. The pattern of acute cyclic AMP accumulation was similar in LH and FSH stimulated granulosa cells, except that the cells were more sensitive to FSH than LH. There was a positive dose response relationship of cyclic AMP accumulation in LH and FSH stimulated cells. LH appeared to partially inhibit FSH stimulated cyclic AMP synthesis. Cyclic GMP accumulation was distinctly different in LH and FSH stimulated cells. An inverse dose response relationship of cyclic GMP to dose LH was observed, with only the lowest dose of LH (0.005 IU/ml) stimulating cyclic GMP synthesis. FSH at 0.005 IU/ml did not stimulate cyclic GMP synthesis, but at higher doses generated cyclic GMP in a positive dose-related manner. The results suggest that specificity of hormone action in granulosa cells may be governed in part by differential on cyclic AMP and cyclic GMP in these cells.

Animals↗