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J W Wilks

Publications and source records attributed to J W Wilks.

16 recordsLinked to original sources
PubMed1992

Visualization of histamine binding to nuclei.

The binding of histamine to cultured microvascular endothelial cells and glycol methacrylate embedded ovarian tissue sections has been localized using fluorescein-albumin-histamine conjugate. Histamine conjugate was bound to the plasma membranes and nuclei of luteal, endothelial, and ovarian stromal cells. An apparent increase in the binding of histamine to nuclei was observed in the presence of cimetidine but the plasma membrane staining was still evident. Unlike cimetidine, pyrilamine completely inhibited the binding of histamine to the plasma membrane. Instead, in the presence of pyrilamine, histamine bound exclusively to the nuclei of endothelial, germinal epithelial, granulosa, and stromal cells. However, the nuclei of terminally differentiated luteal cells and oocytes were not labeled. The functional significance of these nuclear histamine binding sites remains to be determined.

Animals↗
PubMed1991

Isolation and characterization of microvascular endothelial cells from developing corpus luteum.

We have isolated and characterized microvascular endothelial cells from the developing rabbit corpus luteum. The isolated cells express Factor VIII-related antigen and angiotensin-converting enzyme, internalize acetylated low-density lipoprotein, and form capillary-like tubules in collagen gel cultures. Of the mitogens tested, only basic fibroblast growth factor stimulated the proliferation of these cells. Transforming growth factor-beta 1 and tumor necrosis factor-alpha strongly inhibited the proliferation of these endothelial cells. Platelet-derived growth factor, epidermal growth factor, insulin-like growth factor-1, histamine, prostaglandins, sex steroids, and interleukin-6 (interferon-beta 2) had no effect on the proliferation of these microvascular endothelial cells from the corpus luteum, whereas interleukin-1 alpha and 1 beta were mildly inhibitory. Endothelial cells are an essential component of corpus luteum physiology. Therefore, the availability of these cells will allow us to investigate the potential interactions between endothelial cells and luteal cells in vitro.

Animals↗
PubMed1990

Specific inhibition of endothelial cell proliferation by thrombospondin.

Angiogenesis is a multi-step event involving endothelial cell migration, attachment, and proliferation. A thrombospondin (TSP)-like protein has recently been described as a naturally-occurring inhibitor of angiogenesis. We now report that human platelet TSP inhibits the in vitro proliferation of endothelial cells from the rabbit corpus luteum, bovine adrenal cortex and pulmonary artery, and human umbilical vein. The antiproliferative effect of TSP was neutralized by monoclonal antibodies against TSP. The growth arrest seen with TSP was specific for endothelial cells since TSP actually stimulated the growth of vascular smooth muscle cells and human foreskin fibroblasts. These results imply that the angiogenesis-inhibiting effect of TSP is mediated through an inhibition of endothelial cell proliferation. Elucidation of the mechanism of action of TSP on endothelial cell proliferation may lead to potential therapeutic approaches for the control of neovascular diseases.

Animals↗
PubMed1987

Aprotinin antagonizes the binding of human chorionic gonadotropin to its receptor.

Aprotinin caused a dose-dependent inhibition of [125I]hCG binding to its receptor in plasma membranes prepared from luteinized rat ovaries. Displacement of [125I]hCG from its receptor by aprotinin was temperature dependent, with an ID50 of 300 microM at 4 C and an ID50 of 3700 microM at 22 C. Equilibrium binding data showed a decrease in the Ka for hCG in the presence of increasing concentrations of aprotinin; aprotinin had no effect on the number of binding sites. The rate of association of hCG with its receptor was markedly reduced in the presence of aprotinin, but aprotinin had little effect on the rate of dissociation. Control experiments established that aprotinin did not inhibit the binding of [125I]hCG to its receptor due to its lectin properties, an ionic effect or some irreversible impairment of the receptor or hormone. Aprotinin did not inhibit hCG binding when the receptor was solubilized out of ovarian membranes with Triton X-100. Aprotinin inhibited the hCG-mediated activation of adenylate cyclase in rat ovarian plasma membranes in a dose-dependent manner. Similarly, aprotinin antagonized the hCG-stimulated biosynthesis of progesterone by dispersed rat luteal cells. The maximal agonistic activity of hCG was attenuated in these two bioassays. The data are compatible with a hypothesis that aprotinin sterically hinders the entry of hCG into its receptor site by binding to a protease in the plasma membrane that is closely associated with the hCG receptor. This proposal is consistent with the emerging concept that integral membrane proteases are modulators of receptor function.

Animals↗
PubMed1979

Serum FSH, LH and testosterone in the male rhesus following prostaglandin injection.

Adult male rhesus were treated with PGE2, PGF2 alpha or the 13,14-dihydro-15-keto metabolite of PGE2 in a randomized crossover design. Serum concentrations of FSH, LH and testosterone were determined and compared to the respective values in the same uninjected animals. No significant changes were noted in controls or following the metabolite injection. FSH increased gradually for 4 hours after metabolite treatment. In contrast, injection of PGF2 alpha was followed by an abrupt (within 15 minutes) increase in LH and testosterone. FSH increased gradually in 2 of 3 treated animals. Injection of PGE2 was followed by a similar abrupt increase in LH concentration. This was not always associated with a significant increase in testosterone or FSH. These results demonstrate that injections of PGE2 or PGF2 alpha can change serum gonadotropin and testosterone concentrations in male rhesus monkeys, and that the effects of these two prostaglandins are qualitatively different.

Animals↗
PubMed1979

Characterization of the exfoliative antispermatogenic agent 1-(2,4-dichlorobenzyl)-H-indazole-3-carboxylic acid in the rhesus monkey.

The effects of oral doses of 1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxylic acid (DICA) on spermatogenesis in the rhesus monkey (Macaca mulatta) was studied. Four animals given five daily 50 mg/kg doses or three or five daily 500 mg/kg doses showed that DICA was an exfoliating antispermatogenic compound. The inhibition of spermatogenesis was only partially reversible following 500 mg/kg doses of DICA. Weekly and monthly 50 mg/kg doses of DICA only partially inhibiting spermatogenesis as measured by electro-ejaculated sperm counts. Response in individual monkeys ranged from azoospermia to no effect. Testicular biopsies confirmed this finding. DICA did not affect serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), or testosterone concentrations. The blood absorption or urinary excretion rates of uniformly tritiated DICA in the animals that responded well did not differ from those monkeys that responded poorly. DICA metabolites were not detected in monkey urine. Serum testosterone concentrations appeared to vary with the season of the year, but FSH concentrations and ejaculated sperm count did not.

Animals↗
PubMed1977

Luteolytic action of 15-keto prostaglandin F2alpha in the rhesus monkey.

The naturally-occurring metabolite of prostaglandin F2alpha, 15-keto prostaglandin F2alpha (15-keto PGF2alpha), elicited rapid and sustained declines in serum progesterone concentrations when administered to rhesus monkeys beginning on day 22 of normal menstrual cycles. Evidence for luteolysis of a more convincing nature was obtained in studies where a single dose of 15-keto PGF2alpha was given on day 20 of ovulatory menstrual cycles in which intramuscular injections of hCG were also given on days 18-20; serum progesterone concentrations fell precipitously in monkeys within 24 hours following intramuscular administration of 15-keto PGF2alpha. However, corpus luteum function was impaired in only 4 of 11 early pregnant monkeys when 15-keto PGF2alpha was administered on days 30 and 31 from the last menses, a time when the ovary is essential for the maintenance of pregnancy. Gestation failed in 2 additional monkeys 32 and 60 days after treatment with 15-keto PGF2alpha, but progressed in an apparently normal manner in the remaining 5 animals. Two pregnant monkeys treated with 15-keto PGF2alpha on day 42 from the last menstrual period, a time when the ovary is no longer required for gestation, continued their pregnancies uneventfully. Corpus luteum function was not impaired in 9 control monkeys which received injections of vehicle or hCG at appropriate times during the menstrual cycle or pregnancy.

Animals↗
PubMed1976

A new radioimmunoassay for follicle-stimulating hormone in macaques: ovulatory menstrual cycles.

A sensitive and specific radioimmunoassay system for macaque follicle-stimulating hormone (mFSH) was developed utilizing an antiserum (H-31) prepared in a rabbit against purified ovine FSH as the immunogen. Sera from castrated female, adult male, and juvenile rhesus monkeys, as well as urinary extracts from castrated rhesus and bonnet monkeys, were used to demonstrate parallelism with a standard of partially purified monkey pituitary gonadotropins (LER-M-907-D). An extract of baboon pituitary tissue also showed parallelism with the reference standard. A highly purified pituitary extract (WP-X-105-28), containing approximately 75% macaque luteinizing hormone (mLH) and 1% mFSH, was used to demonstrate the specificity of this mFSH assay system. Sera and urinary extracts obtained from hypophysectomized monkeys did not show cross-reactivity in the assay. Macaque chorionic gonadotropin (mCG) did not produce an inhibition curve in the assay, as determined from serum samples and urinary extracts collected from pregnant monkeys at the time of peak mCG secretion. Serum concentrations of mFSH were suppressed in ovariectomized monkeys by the administration of ethinyl estradiol for 3 days, but returned to near pretreatment values by 96 h after the last estradiol administration. The determination of serum mFSH concentrations in daily blood samples obtained from 20 rhesus monkeys throughout ovulatory menstrual cycles revealed a pattern similar to that previously reported for the rhesus monkey and the woman. The peak value of serum mFSH during the menstrual cycle coincided with the midcycle surge of mLH in each case. The gonadotropin peaks were preceded by increasing serum concentrations of estradiol and followed by rises in the serum concentrations of progesterone. The follicular phase of the menstrual cycle was characterized by continuously decreasing serum concentrations of mFSH, reaching a preovulatory nadir 48 h prior to the midcycle mFSH and mLH surges. Serum mFSH concentrations following the midcycle gonadotropin surges decreased progressively as serum progesterone concentrations increased and reached a plateau, and then increased during the last week of the menstrual cycle as corpus luteum function was waning. We have prepared a large pool of antiserum for distribution under the aegis of the Contraceptive Development Branch of the Center for Population Research, the National Institute of Child Health and Human Development.

Animals↗
PubMed1976

Luteal phase defects in the rhesus monkey: the significance of serum FSH:LH ratios.

Luteal phases of an abbreviated duration or suboptimal progesterone secretion were identified in the rhesus monkey. Characterization of menstrual cycles with short luteal phases (8 days) in 5 monkeys revealed the following deviations from normal: a. a failure of serum FSH to decline progressively from an early follicular phase high to a preovulatory nadir; b. a commonly inadequate, or absent, preovulatory FSH surge; c. subnormal serum LH concentrations during both the follicular and luteal portions of the menstrual cycle; d. ratios of serum FSH:LH which did not progressively decrease during the follicular phase; and e. serum estradiol concentrations below normal values during the luteal portion of the menstrual cycle. One monkey had abnormally low serum concentrations of progesterone, although the luteal phase was 19 days in duration. Serum gonadotropin and estradiol patterns in this latter monkey were identical to those observed in monkeys with short luteal phases. It is concluded that inappropriate ratios of serum FSH:LH during the follicular phase of the menstrual cycle result in impaired corpus leteum function. The data document the usefulness of the nonhuman primate for investigating those luteal phase defects which also occur in the woman.

Animals↗
PubMed1976

Peripheral plasma progesterone during egg transport in the rabbit.

Peripheral plasma progesterone concentrations were measured in New Zealand rabbits every 6 hr beginning 12 hr before and continuing until 96 hr after either natural mating, hCG injection, or saline injection. The number of ovulation points in naturally mated animals (9.3 +/- 0.6, mean +/- SE) was not significantly different from that in hCG-injected animals (8.6 +/- 1.5). There was a surge in progesterone secretion following both mating and hCG injection. Plasma progesterone concentrations reached a peak prior to ovulation and then fell to basal levels at the time of ovulation. Beginning at approximately 30 hr after the ovulation-inducing stimulus, there was a progressive, significant (P less than 0.001) increase in plasma progesterone concentration, which continued for the duration of the sampling period. The initiation of the postovulatory increase in progesterone secretion corresponds temporally with the movement of eggs from the ampullary-isthmic junction into the isthmus. The progressive increase in plasma progesterone between 30 and 72 hr after the induction of ovulation corresponds with the gradual movement of eggs through the isthmus into the uterus. The data suggest that movement of eggs through the oviductal isthmus is influenced by the postovulatory secretion of progesterone.

Animals↗
PubMed1975

Prostaglandin F2alpha and human prostatic affinity for testosterone.

Earlier work had shown that the lactogen, LTH and HPL, foster testosterone binding by the prostate. This study was undertaken to see if prostaglandin F2alpha would oppose the effect of the lactogen on the prostate as it does the luteotrophic action of the hormone on the corpus luteum. When it was found instead that the PGF increases steroid binding and that its interaction with lactogen was neither antagonistic nor additive, attention was directed to further characterization of prostaglandin's effect. A dosage/response study of F2alpha alone showed that concentrations of 4 ng/ml and 40 ng/ml increased binding but that 400 ng/ml did not. Glands with stromal hyperplasia and/or inflammation were not responsive than those with epithelial hyperplasia. Assays of water extracts of the tissue revealed concentrations of about 340 ng of F2alpha per gram fresh weight and that the concentration varied inversely as the beta-glucuronidase activity. If the enzyme level is considered an index of the epithelial cell density within the specimen, the inverse relationship suggest a non-epithelial (stromal) site of prostaglandin concentration.

Dose-Response Relationship, Drug↗