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Biomedical subjects

M J Novy

Publications and source records attributed to M J Novy.

At least 37 records · Page 2Linked to original sources
PubMed1994

Prostaglandin production during spontaneous labor and after treatment with RU486 in pregnant rhesus macaques.

The production of prostaglandins from amnion, chorion, decidua, and myometrium was studied in a superfusion system to determine the level of prostaglandin production during late pregnancy, during spontaneous labor, and after in vivo treatment with RU486. Tissues were divided into three groups: those from pregnant control animals, those from animals receiving RU486 (20 mg/kg/day for 3 days) in vivo, and those from animals in spontaneous term labor. Tissues were collected at cesarean section and placed in the superfusion system. After a 30-min equilibration period, fractions of media were collected after passing through the tissue chambers and were assayed for prostaglandin F2 alpha (PGF2 alpha) and prostaglandin E2 (PGE2). The results showed a significant increase in PGF2 alpha from decidua of animals treated with RU486 compared to pregnant controls (pregnant: 3.01 +/- 0.45 ng/g/min; RU486: 4.45 +/- 0.28 ng/g/min; p < 0.05). There was a dramatic increase in PGE2 production by amnion from animals in spontaneous labor but not after RU486 treatment (pregnant: 0.21 +/- 0.06 ng/g/min; RU486: 0.56 +/- 0.09 ng/g/min; spontaneous labor: 5.83 +/- 0.43 ng/g/min; p < 0.01). We conclude that while progesterone is important for maintaining uterine quiescence during pregnancy, progesterone receptor blockade by RU486 does not lead to an increase in PGE2 production by amnion as is shown during normal spontaneous labor.

Amnion↗
PubMed1993

Plasma oxytocin and nocturnal uterine activity: maternal but not fetal concentrations increase progressively during late pregnancy and delivery in rhesus monkeys.

OBJECTIVE: The purpose of the study was to determine whether rising maternal or fetal plasma oxytocin concentrations could be responsible for the increasing levels of nocturnal uterine activity on the nights preceding delivery. STUDY DESIGN: Chronically catheterized pregnant rhesus monkeys were exposed to a 16-hour light, 8-hour dark photoperiod (dark 11 PM to 7 AM). Uterine activity and maternal arterial plasma oxytocin concentrations were measured concurrently at weekly intervals in late gestation, on the night preceding term delivery (158 to 167 days, n = 4), and during delivery (149 to 170 days, n = 6). Fetal carotid arterial plasma oxytocin levels were measured during episodes of nocturnal uterine activity in six animals. The effect of oxytocin infusions into the fetus (30 to 480 ng/kg/hr) on uterine activity and on maternal and fetal plasma oxytocin levels was also determined (n = 3). RESULTS: Maximal nocturnal oxytocin concentrations in the maternal plasma rose progressively during late gestation from 9.9 +/- 3.5 pg/ml at 130 to 139 days to 28.7 +/- 9.8 pg/ml on the night preceding term delivery (p < 0.005); a significant increase in nocturnal uterine activity accompanied this rise (p < 0.001). Maternal oxytocin concentrations were elevated during labor and increased further at delivery (62.5 +/- 5.5 pg/ml, p < 0.05). There was no increase in fetal plasma oxytocin during nocturnal uterine activity (3.1 +/- 0.2 pg/ml) or during labor. Fetal oxytocin infusions raised fetal plasma oxytocin concentrations sixtyfold but had no effect on maternal plasma oxytocin concentrations or on uterine activity. CONCLUSIONS: Elevated maternal plasma oxytocin concentrations are responsible, at least in part, for the increasing magnitude of nocturnal uterine activity episodes as term approaches and for the elevated uterine activity before delivery at night. Fetal plasma oxytocin does not contribute to nocturnal uterine activity or to maternal plasma oxytocin concentrations.

Animals↗
PubMed1993

Progesterone receptor messenger ribonucleic acid and protein are overexpressed in human uterine leiomyomas.

OBJECTIVE: Our purpose was to identify molecular mechanisms underlying abnormal growth of uterine leiomyomas. STUDY DESIGN: Biopsy samples of tumor and adjacent "normal" myometrium from nine patients were analyzed for progesterone receptor gene expression and for proliferation-associated antigen Ki-67. RESULTS: Northern analysis indicated that progesterone receptor messenger ribonucleic acid levels were increased twofold to 15-fold in leiomyoma compared with adjacent myometrial biopsy tissue from all patients (n = 9), whereas beta-actin messenger ribonucleic acid was at similar levels in these samples. Quantitative immunoassay, immunohistochemistry studies, and Western blot analyses revealed increased amounts of progesterone receptor protein in the tumor tissue. Both the progesterone receptor A and B forms were expressed in the leiomyoma and adjacent myometrium. Corresponding to increased progesterone receptor gene expression, the proliferation-associated antigen Ki-67 was also significantly elevated in the leiomyoma tissue. CONCLUSION: These data provide the first evidence that progesterone receptor messenger ribonucleic acid is overexpressed in uterine leiomyomas, suggesting that amplified progesterone-mediated signaling is instrumental in the abnormal growth of these tumors.

Adult↗
PubMed1992

Intrauterine insemination outperforms intracervical insemination in a randomized, controlled study with frozen, donor semen.

OBJECTIVE: To assess the efficacy of intrauterine insemination (IUI) in a donor insemination program. DESIGN: Prospective randomized clinical trial. SETTING: Donor insemination program. PATIENTS, PARTICIPANTS: Women undergoing insemination were randomly assigned to receive either IUI or intracervical insemination for a maximum of six cycles. INTERVENTIONS: None. MAIN OUTCOME MEASURE(S): Cycle fecundity rates between the two routes were compared. RESULTS: The monthly fecundity rate for intracervical insemination was 5.1% compared with 23% by IUI. By life table analysis, pregnancy rates for IUI were significantly higher than intracervical insemination (P = 0.02). CONCLUSIONS: Intrauterine insemination with quarantined donor sperm is superior to intracervical insemination.

Cervix Uteri↗
PubMed1992

Fetal and maternal endocrine responses to reduced uteroplacental blood flow.

In clinical practice, falling or reduced maternal estrogen levels are commonly regarded as indicators of fetal distress. However, experimental studies in primate animal models demonstrate that changes in maternal estradiol concentrations vary in response to reduced uteroplacental blood flow and are elevated during fetal hypoxemic stress, suggesting an increase in fetal adrenal precursor steroids. We studied the effects of graded reductions in maternal distal aortic blood flow (Qda) on the fetal MCR of dehydroepiandrosterone (D; MCR-D), the fetal production rate of D (PR-D), and changes in maternal and fetal plasma concentrations of D, D sulfate, cortisol, androstenedione, estrone (E1), and estradiol (E2) and in fetal plasma ACTH, PRL, and LH. A continuous i.v. infusion of [7-3H]D was administered to fetuses in five pregnant baboons (Papio anubis) at 155-165 days gestation (term, 184 days) for 270 min. A 50% reduction in mean distal aortic blood flow was imposed after 60 min by means of partial occlusion of the aorta with a snare device, which was released at 180 min. Maternal and fetal blood samples were collected at 10-min intervals from 30-60, 120-180, and 240-270 min. Equilibrium concentrations of [3H]D in fetal plasma were determined, and the MCR-D and PR-D were calculated for each of the three levels of Qda corresponding to the control, occlusion, and release intervals. Concentrations of steroid and peptide hormones in maternal and fetal plasma were determined by RIA, and arterial blood pH, pO2, and pCO2 were measured. Control fetal PR-D (mean +/- SE, 4.4 +/- 2.0 mg/day) rose significantly during aortic occlusion accompanied by fetal hypoxemia (11.8 +/- 3.1 mg/day; P less than 0.05) and remained elevated with release of the aortic constriction (13.8 +/- 2.9 mg/day). Changes in fetal MCR-D were variable and not statistically significant. Among the maternal plasma steroids, only E1 and E2 increased significantly, doubling from control values during aortic occlusion and increasing by another 50% after release (P less than 0.05). There was a significant correlation between fetal PR-D and maternal plasma E2 and E1 concentrations (r2 = 0.76 and 0.71, respectively; P less than 0.01). Fetal hypoxemia was associated with dramatic increases in fetal plasma D, D sulfate, androstenedione, E1, and E2. No significant change occurred in fetal plasma cortisol, which tended to decline throughout the study. We observed a dramatic and sustained increase in fetal plasma ACTH during the period of reduced Qda and for 90 min thereafter, but no change in PRL or LH.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenocorticotropic Hormone↗
PubMed1992

Steroid hormone receptors in the adrenal glands of fetal and adult rhesus monkeys.

Sex steroid hormone receptors have been identified in the adrenal glands of rodents and may have a role in adrenal function. The highly estrogenic environment during pregnancy has been proposed to influence steroidogenesis by the fetal zone of the primate fetal adrenal gland. In order to determine whether these effects involve receptor-mediated mechanisms, we have examined the concentration and distribution of estrogen receptor (ER), androgen receptor, and progesterone receptor (PR) in the adrenal glands of fetal, immature, and adult rhesus monkeys. Monoclonal antibodies were used for immunocytochemistry (ICC), and in a gradient shift assay, for determination of receptor distribution and concentrations, respectively. There was no difference between the concentrations of ER in the adrenal glands from male and female adult animals (12.4 +/- 2.2, n = 3 and 13.2 +/- 2.0 fmol/mg DNA, n = 7; respectively); however, the concentration of ER in the fetal adrenal glands was markedly lower than in the adults (combined adult 12.7 +/- 1.6, n = 10, and fetal 0.9 +/- 0.4 fmol/mg DNA, n = 7; P less than 0.01). The concentration of ER in the adrenal glands of immature animals was also lower compared to adult animals (6.1 +/- 1.6, n = 6, P less than 0.05). In the adult, ICC revealed that staining for ER was restricted to the cell nucleus and was most dense in the zone fasciculata, with lesser staining in the zona glomerulosa and zona reticularis, and with no detectable staining in the medulla. ER staining was virtually absent in the fetal zone which comprises the major portion of the fetal gland; however, some staining was observed in the narrow definitive zone. The distribution of androgen receptor was similar to that of ER, whereas there was no detectable staining for PR in the adrenals of either adult or fetal animals. We conclude: 1) that the lower concentration of ER in fetal adrenal glands is due to the absence of ER in the fetal zone; 2) the lack of ER and PR in the fetal zone suggests that estrogens and progestins do not influence the growth or function of the fetal zone by receptor-mediated mechanisms; 3) estrogens and androgens may influence the function of the adult adrenal cortex.

Adrenal Glands↗
PubMed1991

Transabdominal cervicoisthmic cerclage: a reappraisal 25 years after its introduction.

Most cerclage operations for cervical insufficiency are performed transvaginally. The transabdominal route is beneficial in treating patients with cervices that are either extremely short, congenitally deformed, deeply lacerated, or markedly scarred because of previously failed transvaginal cerclage procedures. The average gestational age at surgery was 11.5 weeks and the operation was performed after early ultrasonographic verification of fetal viability. Patients with advanced cervical effacement or dilatation in the second trimester were excluded. A 5 mm wide Mersilene band was applied in an avascular space above the junction of the cervix and the uterine isthmus without dissection or tunneling among broad ligament vessels. This simplified surgical approach resulted in little operative blood loss (mean, 75 ml; range, 50 to 200 ml). After transabdominal cervicoisthmic cerclage, 21 pregnancies in 20 patients resulted in 18 term births, one premature birth with favorable outcome, and two early fetal deaths (90% salvage rate). A review of the world literature indicated 130 pregnancies with transabdominal cervicoisthmic cerclage during pregnancy and a cumulative success rate of 89%. Preconceptional transabdominal cervicoisthmic cerclage was reported in 30 pregnancies with an overall fetal survival rate of 81%. A survey of specialists in maternal-fetal medicine indicated an increasing interest and familiarity with transabdominal cervicoisthmic cerclage since its introduction more than two decades ago although this procedure is still not widely applied in obstetric practice.

Abdomen↗
PubMed1991

Endocrine and morphological maturation of the fetal and neonatal adrenal cortex in baboons.

Developmental changes in basal and circadian fluctuations in plasma dehydroepiandrosterone sulfate (DHEAS) and cortisol (F) from birth until 3 months of life were studied in conjunction with morphological characteristics of the fetal and neonatal adrenal cortex in baboons (Papio anubis). These studies were complimented by measurements of in vitro production of DHEAS and F (basal and ACTH stimulated) by adrenal tissue slices. Cortisol, DHEAS, estrone, estradiol, and progesterone were determined in plasma and incubation medium by specific RIA. After delivery, an initial rise in plasma DHEAS was sustained for 4 days, followed by a precipitous decline, which reached a nadir between days 10-12 postpartum. Thereafter, plasma DHEAS and F concentrations stabilized with minor fluctuations. A significant (P less than 0.05) and persistent diurnal rhythm in DHEAS and F secretion was evident by the end of the first week after birth. Administration of estrone acetate and progesterone in oil maintained neonatal plasma concentrations of estrone, estradiol, and progesterone at levels comparable to those in utero, but had no quantitative or qualitative effect on the pattern of plasma DHEAS or F in the neonate. The relative production of F to DHEAS by tissue slices in vitro (the calculated F/DHEAS ratios) indicates that DHEAS secretion by the fetal adrenal is 10-fold higher than that of F near parturition; ACTH stimulation does not alter this relationship. By postnatal day 10, the basal production rates of F and DHEAS are equivalent, and the response to ACTH stimulation favors production of F. With advancing neonatal age (at 30 and 100 days), there is an increase in the F/DHEAS secretion ratio both during the basal state and in response to ACTH. The baboon adrenal glands increased in weight during the last month of gestation and then stabilized during the early postnatal period; a gradual increase in weight was observed after 30 days postpartum. Within 2 weeks after parturition, the relative width of the fetal zone decreased dramatically to occupy less than one third of the total cortex. During involution, we observed a decrease in cell size and a reduction in cytoplasmic vacuolation. A zone of closely packed cells with numerous areas of cell death (the dense band) separated the zona fasciculata from the fetal zone. Cell proliferation was observed in the upper regions of the definitive cortex. We conclude the following. 1) The hypothalamic-hypophyseal mechanisms that regulate the diurnal adrenal secretory rhythm are established in the early neonatal period in the baboon.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Cortex↗
PubMed1991

Comparison of plasma oxytocin and catecholamine concentrations with uterine activity in pregnant rhesus monkeys.

Pregnant rhesus monkeys exhibit diurnal changes in uterine activity (UA), with episodes of increased UA during the early hours of darkness. The estrogenic environment during late pregnancy serves a permissive role in the maintenance of nocturnal UA episodes and may involve myometrial interactions with oxytocin (OT) and/or alpha-adrenergic stimuli. In the present study we have used chronically catheterized pregnant rhesus monkeys to measure diurnal changes in maternal plasma OT, epinephrine, norepinephrine, and dopamine. We also determined the effects of infusing an OT antagonist (ORF 22164) and the alpha-adrenergic antagonist phentolamine on nocturnal UA episodes. Animals were exposed to a 16-h light, 8-h dark photo-period, with the hours of darkness between 2300-0700 h. Maternal plasma samples were collected at 3-h intervals for 36 h and analyzed by RIA for OT and by high performance liquid chromatography for catecholamines. Plasma OT was correlated with UA in animals that displayed nocturnal UA episodes (r = 0.76; P less than 0.01). Maximal OT concentrations occurred at 2400 h in these animals; plasma OT was higher during the hours of darkness compared to levels during the light phase (10.4 +/- 1.9 and 3.0 +/- 0.3 pmol/L, respectively; n = 4). Some animals did not display nocturnal episodes of increased UA and showed no increase in OT concentrations during the hours of darkness. Maternal plasma catecholamine concentrations were not correlated with nocturnal UA and were maximal during the light phase. Nocturnal UA was abolished within 30 min of infusion of the OT antagonist, but phentolamine infusions had no effect on nocturnal UA. We conclude that 1) changes in maternal plasma catecholamine concentrations are not involved in the generation of nocturnal UA; 2) the presence of episodes of increased UA at night results from increased maternal plasma OT concentrations; and 3) the absence of nocturnal UA in some animals can be explained by a reduced level of OT secretion.

Animals↗
PubMed1991

Antagonism of oxytocin in rats and pregnant rhesus monkeys by the novel cyclic hexapeptides, L-366,682 and L-366,948.

Two cyclic hexapeptides unrelated in chemical structure to oxytocin (OT) were shown in vivo to be antagonists of the contractile action of OT on the uterus. In anesthetized rats challenged with OT (1 micrograms/kg) administered as an i.v. bolus, L-366,682 [cyclo-(L-Pro-D-Trp-L-Ile-D-pipecolic acid-L-pipecolic acid-D-His)] and L-366,948 (D-2-naphthyl-alanine in place of D-Trp) were equipotent with AD50 values of about 100 micrograms/kg i.v. At doses of L-366,682 or L-366,948 causing approximately 90 to 95% block (approximately the AD95 dose) of OT, the duration of action of the antagonists exceeded 145 min. Both compounds exhibited selectivity in the rat, as a dose of either at 300 micrograms/kg i.v. shifted the dose-response for OT-induced uterine contraction to the right by approximately 5-fold but did not affect the dose-response to prostaglandin F2 alpha. Furthermore, neither compound, at a dose of 3 mg/kg i.v., antagonized the action of arginine vasopressin acting at V-1 (pressor effect in pithed rats) or V-2 (antidiuretic) receptors. In conscious, freely moving, pregnant rhesus monkeys, L-366,948 or L-366,682 given i.v. or s.c. were effective antagonists of uterine contractions elicited by an infusion of OT. OT- or arginine vasopressin-like agonist activity was not observed in any of the in vivo models. It is concluded that L-366,682 and L-366,948 act in vivo as reasonably potent, long-acting and selective antagonists at OT receptors in the rat and rhesus uterus.

Animals↗
PubMed1990

Shirodkar cerclage in a multifactorial approach to the patient with advanced cervical changes.

Patients with a markedly effaced or dilated cervix and protruding membranes between 21 and 26 weeks' gestation were managed by Shirodkar cervical cerclage, perioperative tocolysis, broad-spectrum antibiotic therapy, and, in selected cases, inhibition of prostaglandin synthesis with indomethacin. The average duration of pregnancy after cerclage in nine patients was 11.8 weeks (range, 1 to 18 weeks). The mean birth weight was 2456 gm (range, 810 to 4341 gm). Eight of the nine pregnancies resulted in live infants (fetal survival rate, 89%); six patients (66%) were delivered at or near term. Preterm delivery occurred at 28 and 35 weeks' gestation in two patients and premature rupture of the membranes occurred in another at 25 weeks, 5 days after cerclage. There was no maternal postoperative or postpartum morbidity. A multifactorial approach to the patient with advanced cervical changes and protruding membranes in the second trimester resulted in a high rate of fetal survival and prolongation of pregnancy until term in the majority of patients. The Shirodkar cerclage holds a distensible cervix closed while the adjunctive medical therapy restores homeostasis.

Anti-Bacterial Agents↗
PubMed1990

Amniotic fluid lipoxygenase metabolites during spontaneous labor and after RU486 treatment during late pregnancy in rhesus macaques.

To determine changes in amniotic fluid (AF) lipoxygenase metabolites prior to spontaneous labor and after RU486 administration, we implanted AF and vascular catheters and myometrial electromyographic (EMG) electrodes in 8 rhesus macaques at 120-130 days of pregnancy (term = 167 days). Four animals had AF samples taken serially until they delivered their infants normally at term. The other four animals received RU486 (20 mg/kg/day) for 3 days. AF samples were collected every 2-3 days and at 12 hour intervals for 72 hours before and after treatment with RU486. Uterine activity was monitored continuously. LTB4, 5-HETE and 15-HETE were measured by radioimmunoassay. In untreated animals, LTB4 and 5-HETE concentrations in AF increased significantly (P less than 0.05) 4 days before delivery with no change in 15-HETE. After RU486, mean levels of LTB4 and 5-HETE were increased although the difference was not statistically significant. No change in 15-HETE levels was observed. In conclusion, LTB4 and 5-HETE increase in AF before the onset of spontaneous labor. Progesterone receptor blockade by RU486 does not reproduce the changes in AF lipoxygenase metabolites observed during normal parturition.

Amniotic Fluid↗
PubMed1990

A comparative evaluation of intracervical and intrauterine routes in donor therapeutic insemination.

The relative efficiency of intrauterine insemination with washed spermatozoa versus intracervical deposition of semen was examined in donor insemination for therapeutic reasons. Fecundability in a group of 26 women who desired insemination as a treatment for azoospermia or severe astheno-oligozoospermia in their partner was comparable, despite the 10-fold higher numbers employed using the intracervical route.

Cervix Uteri↗
PubMed1990

Uterine estrogen receptors are increased by RU486 in late pregnant rhesus macaques but not after spontaneous labor.

Progesterone withdrawal as a mechanism for parturition in primates is controversial. The progesterone antagonist RU486, given in late pregnancy to rhesus monkeys at a dose of 47 mmol/kg.day (20 mg/kg.day), causes an increase in uterine activity, but not the expected increase in amniotic fluid prostaglandins or cervical dilatation. We, therefore, studied the effect of RU486 on estrogen receptor (ER) localization and concentration in reproductive tract tissues in rhesus monkeys during late gestation and after spontaneous labor at term. Distribution of ER in pregnant uterine tissues was studied by immunocytochemical techniques and quantified by a biochemical assay, both of which employed a monoclonal antibody specific for ER. ER was not present in amnion and chorion by immunocytochemical investigation; however, a significant increase in receptor staining was seen in decidua and myometrium after RU486 treatment compared to that in both pregnant control tissues and parturient tissues. Sucrose gradient assay of nuclear (n) and cytosolic (c) ER revealed a low level of ER (expressed as fmol of estradiol bound/mg of DNA) in pregnant and parturient decidua (pregnant: nER = 7.3 +/- 2.4, cER = 17.1 +/- 6.4; parturient, nER = 7.7 +/- 3.1, cER = 16.4 +/- 8.8) and myometrium (pregnant: nER = 21.7 +/- 4.1, cER = 20.8 +/- 5.3; parturient: nER = 30.0 +/- 2.8, cER = 10.7 +/- 6.7). In contrast, tissues collected from RU486-treated animals contained high levels of ER in decidua (nER = 52.3 +/- 16.8, cER = 240.5 +/- 145.3) and myometrium (nER = 77.0 +/- 19.2; cER = 66.5 +/- 31.6). We conclude that 1) the increase in ER in decidua and myometrium after RU486 treatment is the result of a decrease in the inhibitory action of progesterone on ER and documents the progesterone receptor antagonism by RU486 during induced myometrial contractility in late pregnant rhesus monkeys; 2) the absence of ER from amnion and chorion indicates that the normally observed increase in prostaglandin production by rhesus fetal membranes during labor is not mediated by ER; and 3) the absence of a change in the concentration of ER in decidua and myometrium from pregnant control monkeys and those in spontaneous labor indicates that an increase in ER (and, by inference, a withdrawal of receptor-mediated progesterone inhibition) is not part of the normal events in preparation for parturition in primates.

Amnion↗
PubMed1990

Serial beta-hCG measurements in the early detection of ectopic pregnancy.

We investigated the sensitivity and specificity of serial serum hCG assays to diagnose early ectopic pregnancy in 50 asymptomatic women at risk. The initial two hCG values obtained at 2-5-day intervals were used to calculate doubling time and percentage increase. Twenty-five women had a viable intrauterine pregnancy, 14 an ectopic gestation, ten a spontaneous abortion, and one a molar pregnancy. A normal percentage increase and/or doubling time was observed in 64% of women who eventually proved to have an ectopic pregnancy. Ultimately, 85% of our patients demonstrated abnormal values when subsequent hCG pairs were analyzed. The sensitivity of these tests to diagnose asymptomatic ectopic pregnancy was 36%, with a specificity of 63-71%. We conclude that a normal rise in hCG production does not reliably differentiate an ectopic from an intrauterine pregnancy in the asymptomatic patient.

Chorionic Gonadotropin↗
PubMed1989

Half-life of plasma sex steroid-binding protein (SBP) in the primate.

We have recently shown that the metabolic clearance of testosterone in plasma is directly dependent on sex steroid-binding protein (SBP or SHBG) levels [J. steroid. Biochem. 22, 739 (1986)]. In order to further understand the relationship between these two parameters, we have measured the half-life of SBP in plasma of female rhesus monkeys. SBP was purified to homogeneity from pooled Macaca nemestrina serum, and iodinated with 125I. The labeled protein ([125I]nSBP) was purified by chromatography on DEAE-agarose and fractions identified as immunologically reactive against anti-human SBP were collected. Protein purity of [125I]nSBP was established by SDS gel electrophoresis using an unlabelled Macaca nemestrina SBP as standard. The labeled protein was infused intravenously into two different adult female Macaca mulatta (rhesus) monkeys. Plasma samples were collected at short intervals during the first 24 h after infusion, and then daily for 7-9 days. The clearance profile of labeled SBP in plasma was quantitated by radioactivity measurement and immunoprecipitation. Analysis of the results indicate that the rate of SBP clearance in plasma has two components, the t1/2 (app) of the first component is 7.5 h (r = 0.94), and the t1/2 (app) of the second component is 3.95 days (r = 0.95). Over 90% of the injected 125I-nSBP was removed from plasma within 24 h at a rate corresponding to the t1/2 (app) of the first component. The data indicate that most of the SBP rapidly distributes into extravascular spaces during the first 24 h following infusion, and are consistent with the hypothesis that SBP may be directly involved in sex steroid hormone transport into tissues.

Animals↗