PubMed Health⌕ Search

Biomedical subjects

M A Fritz

Publications and source records attributed to M A Fritz.

At least 37 records · Page 2Linked to original sources
PubMed1996

Endometrial progesterone receptors and markers of uterine receptivity in the window of implantation.

OBJECTIVE: To compare the expression of endometrial P receptors (PR) levels with markers of endometrial receptivity during the window of implantation. DESIGN: Prospective, controlled study to examine endometrial PR and three cycle-specific integrins in endometrial biopsies obtained during the window of implantation. SETTING: An academic teaching hospital. PATIENTS: One hundred seventy-five endometrial biopsies from regularly cycling women with luteal phase defect (LPD; group 1; n = 80), medically treated LPD (group 2; n = 16), minimal and mild endometriosis with aberrant alpha v beta 3 expression (group 3; n = 21), fertile controls (group 4; n = 26), and infertile controls (group 5; n = 32). MAIN OUTCOME MEASURE: Immunohistochemical staining intensity of each antigen using the semi-quantitative grading system (HSCORE), compared using analysis of variance with Scheffe's correction. RESULTS: Among the five groups studied, nuclear PR expression was significantly elevated in glandular epithelial cells from tissue samples with histologic delay > or = 3 days consistent with luteal phase deficiency (LPD; group 1). Failure of PR down-regulation was associated with aberrant alpha v beta 3 integrin expression. Medical correction of LPD was associated with return of normal endometrial histology, normal integrin expression, and the loss of epithelial PR, similar to controls. The other two cycle-dependent integrin markers, alpha 1 beta 1 and alpha 4 beta 1, were not different between groups. In women with aberrant alpha v beta 3 and "in phase" endometrium, epithelial PR expression was not different from controls. CONCLUSIONS: The establishment of normal endometrial receptivity appears to be tightly associated with the down-regulation of epithelial PR. Histologic delay, consistent with LPD, is associated with a failure of PR down-regulation and the lack of normal markers of endometrial receptivity. Occult uterine receptivity defects (aberrant beta 3 expression in otherwise normal histology) are regulated differently, suggesting alternate mechanisms also exist which influence endometrial receptivity.

Adult↗
PubMed1996

The effect of oral contraceptive pills on markers of endometrial receptivity.

OBJECTIVE: To determine if oral contraceptive (OC) usage alters expression of integrins associated with endometrial receptivity. DESIGN: Immunohistochemical staining intensity for integrins was compared in frozen sections of endometrial tissue specimens obtained from women with normal ovulatory cycles (n = 23; cycle days 20 to 24 based on LH surge) and from those taking oral contraceptives pills (n = 23; cycle days 5 to 27). SETTING: University-based outpatient infertility clinic. RESULTS: Constitutive integrin expression in the endometrium (alpha 2 beta 1, alpha 3 beta 1, alpha 5 beta 1, alpha 6 beta 1, and alpha 6 beta 4) was similar in OC users and normally cycling individuals, except for an increase in epithelial alpha 3 beta 1 in OC users. Oral contraceptive use was associated with significant alterations in cycle-dependent integrin expression (alpha 1 beta 1, alpha 4 beta 1, and alpha v beta 3). Specifically, we observed increased glandular alpha 4 beta 1, and decreased alpha v beta 3 expression. The P-regulated alpha 1 subunit was present in both groups. Increased stromal alpha v and beta 3 and decreased alpha 3 beta 1 and alpha 6 beta 1 staining was observed in OC users. CONCLUSIONS: Expression of those integrins most closely associated with endometrial receptivity, alpha v beta 3 and alpha 4 beta 1, is altered in the glandular epithelium of women taking OCs. Stromal integrin expression in OC users also differs from that in cycling women. These alterations in epithelial and stromal integrin expression suggest that impaired uterine receptivity is one mechanism whereby OCs exert their contraceptive actions.

Adult↗
PubMed1996

Characteristics of gonadotropin response, follicular development, and endometrial growth and maturation across consecutive cycles of clomiphene citrate treatment.

OBJECTIVE: To examine the patterns of gonadotropin response, follicular development, and endometrial growth and maturation across consecutive cycles of clomiphene citrate (CC) treatment. DESIGN: Prospective analysis of cycle characteristics. SETTING: Academic tertiary medical center. PATIENTS: Nineteen consenting anovulatory infertile women receiving standardized, cyclic, incremental treatment with CC (50 to 150 mg/d, cycle days 5 to 9) for ovulation induction. INTERVENTIONS: In each of up to six consecutive treatment cycles, urinary LH was monitored twice daily from cycle day 10 until detection of the LH surge or day 21; blood samples and transvaginal ultrasound (US) examination were obtained on cycle days 3, 10, and every 1 to 3 days thereafter until collapse of the dominant follicle. Endometrial biopsy was performed 11 to 13 days after the LH surge in the first, third, and sixth ovulatory cycle. RESULTS: Follicular phase duration, peak follicular diameter, the number of preovulatory follicles, and peak endometrial thickness and echo pattern remained consistent across consecutive ovulatory (n = 55) and anovulatory (n = 23) treatment cycles. Endometrial dating was > or = 3 days out of phase in 2 of 31 (6%) cycles sampled. Peak serum E2 and P concentrations did not vary with cycle number or correlate with endometrial thickness or echo pattern. Cycle day 10 FSH levels were significantly higher in ovulatory subjects than in anovulatory subjects. CONCLUSIONS: Patterns of gonadotropin response, follicular development, and endometrial growth and maturation remain consistent across consecutive cycles of CC treatment.

Adult↗
PubMed1995

Combined abdominal-perineal sonography to assist in diagnosis of transverse vaginal septum.

BACKGROUND: Transperineal sonography has been used to detect incompetent cervices, placenta previa, cervical pregnancy, and vaginal and cervical atresia. CASE: Transperineal sonography was used to investigate primary amenorrhea in a 14-year-old girl. A mid-transverse septum was found and confirmed surgically. CONCLUSION: Transperineal or translabial sonography assisted in the differentiation of primary amenorrhea, when adequate vaginal access was prohibited.

Abdomen↗
PubMed1993

Effects of individual and combined treatment with prostaglandins E2 and F2 alpha on progesterone secretion by ovine luteal cells supplemented with homologous serum lipoproteins in vitro.

Prostaglandin F2 alpha (PGF2 alpha) is a potent luteolysin, whereas prostaglandin E2 (PGE2) is generally luteotropic in vivo. To establish a model system for investigations of the mechanisms involved in these actions, we examined the effects of individual and combined treatment with PGE2 and PGF2 alpha on basal and ovine LH-stimulated progesterone secretion during long-term incubations conducted with and without supplemental homologous low-density lipoprotein (LDL) as substrate. Effects of both PGF2 and PGF2 alpha were concentration- and time-dependent and were further influenced by the presence of LDL and/or LH in medium. Neither of the prostaglandins exerted any significant effect before 48 h in culture, but distinctly different patterns of response to PGE2 and PGF2 alpha emerged thereafter. Low, but not high, concentrations of PGE2 increased progesterone secretion in the absence of LH, whereas PGF2 alpha (alone and in combination with PGE2) inhibited progesterone production in all medium formulations. The transcriptional inhibitor actinomycin effectively blocked the actions of PGF2 alpha, but had no effect on response to LH or PGE2. These data demonstrate that both the putative luteotropic actions of PGE2 and the potent, luteolytic effects of PGF2 alpha in vivo can be reproduced in long-term cultures of ovine luteal cells in vitro, and they suggest that the mechanism of PGF2 alpha-induced luteolysis may involve new protein synthesis.

Animals↗
PubMed1993

Effects of substrate supplementation with hydroxycholesterol analogues and serum lipoproteins on ovine luteal cell progesterone secretion in vitro: demonstration of prostaglandin F2 alpha luteolytic actions in a defined model system.

In an attempt to establish a defined model system for studies aimed at elucidating the mechanism of PGF2 alpha action, we examined the effects of medium supplementation with soluble hydroxycholesterol analogues, alone and in combination with ovine luteinizing hormone (oLH) in the presence and absence of PGF2 alpha, on progesterone secretion by mixed ovine luteal cells in vitro. In short-term cultures (2-6 h), supplementary 22R-hydroxycholesterol (22R-OHC; 0.16-20 micrograms ml-1) increased (P < 0.05) progesterone production in a dose-dependent manner, whereas similar concentrations of 22S-hydroxycholesterol (22S-OHC) and 25-hydroxycholesterol (25-OHC) had little effect. In incubations of < or = 24 h duration, 22R-OHC (1 micrograms ml-1) dramatically increased progesterone secretion, whereas oLH (100 ng ml-1) in the presence or absence of PGF2 alpha (250 ng ml-1) had no consistent effects, alone or in combination with 22R-OHC. In contrast, 22R-OHC (1 micrograms ml-1) alone had no effect in long-term incubations (72-192 h), nor did treatment with oLH (100 ng ml-1) in the presence or absence of PGF2 alpha (250 ng ml-1) in the absence of 22R-OHC. Together, however, 22R-OHC and oLH stimulated (P < 0.05) progesterone secretion, a synergistic effect consistently inhibited (P < 0.05) by PGF2 alpha. Equimolar (2.5 mumol l-1) concentrations of 22R-OHC and homologous serum low- or high-density lipoprotein cholesterol exhibited comparable capacities to maintain progesterone secretion in long-term cultures (24-168 h), with and without gonadotrophin (oLH or human chorionic gonadotrophin, 100 ng ml-1) stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Influence of corpus luteum age on the steroidogenic response to exogenous human chorionic gonadotropin in normal cycling women.

OBJECTIVE: The null hypothesis of this study is that the patterns of steroid secretion exhibited by the human corpus luteum in response to exogenous human chorionic gonadotropin stimulation are independent of corpus luteum age at the time of treatment. STUDY DESIGN: Twenty-five normally cycling women in whom the midcycle urinary luteinizing hormone surge (luteal day 0) was identified and from whom blood samples were obtained daily from cycle day 11 until menses were prospectively randomized to receive no treatment (group I, n = 5) or exogenous human chorionic gonadotropin 5000 IU administered intramuscularly on luteal day 0 (group II, n = 5), +4 (group III, n = 5), +8 (group IV, n = 5), or +12 (group V, n = 5). Serum concentrations of estrone, estradiol, progesterone, 17-hydroxyprogesterone, and androstenedione were measured by specific radioimmunoassays in all subjects; serum human chorionic gonadotropin concentrations were determined by immunoradiometric assay in treated subjects. RESULTS: Serum human chorionic gonadotropin levels (mean +/- SEM) were virtually identical among treatment groups (p greater than 0.05). Luteal phase duration (mean +/- SEM) was prolonged (p less than 0.05) only in group V (18.4 +/- 0.5 days) compared with untreated subjects (group I 13.8 +/- 0.7 days). In all groups estrone and 17-hydroxyprogesterone concentrations closely paralleled those of estradiol and progesterone, respectively. Steroid data and progesterone/estradiol ratios (mean +/- SEM) in groups I and II were indistinguishable and were combined (control, n = 10). Group III subjects exhibited patterns of steroid secretion similar to groups I and II, although progesterone was moderately increased after human chorionic gonadotropin treatment. In groups IV and V, progesterone increased (p less than 0.05) 1 day after human chorionic gonadotropin and remained elevated for 5 to 6 days; a 4-day rise (p less than 0.05) in estradiol began 3 days after treatment, and androstenedione rose modestly in parallel. Progesterone/estradiol ratios in groups III through V increased (p less than 0.05) approximately twofold after human chorionic gonadotropin treatment and remained elevated for 4 to 5 days. CONCLUSION: The human corpus luteum exhibits distinct age-dependent patterns of steroid secretion in response to exogenous human chorionic gonadotropin stimulation, an observation that may have clinical implications regarding the empirical use of exogenous human chorionic gonadotropin in support of luteal function.

Adult↗
PubMed1992

Onset and characteristics of the midcycle surge in bioactive and immunoactive luteinizing hormone secretion in normal women: influence of physiological variations in periovulatory ovarian steroid hormone secretion.

Limited studies in nonhuman primates suggest that the midcycle LH surge is characterized by distinctly different patterns of bioactive (LH-BIO) and immunoactive (LH-RIA) LH secretion. To further examine the patterns of midcycle LH-BIO and LH-RIA secretion and explore the influence of physiological variations in steroid hormone feedback on LH surge dimensions we studied seven normal ovulatory women over the periovulatory interval. In each, blood samples were obtained every 3 h and transvaginal ultrasonography was performed every 12 h over a 5-7 day interval at midcycle. Serum levels of LH-RIA, FSH, estradiol (E2), progesterone (P4), and 17-hydroxyprogesterone were determined by RIA; LH-BIO was estimated using a mouse leydig cell bioassay. Hormone data were standardized to the time of surge onset in LH-RIA (time zero), defined as a 100% increase above a 6-point running mean baseline value; surge cessation was defined as a decline to below baseline concentration. Mean LH-RIA surge duration was 54.0 +/- 4.0 h. LH-BIO surge onset was simultaneous with that of LH-RIA and coincident with the peak in E2 levels (mean data). Mean P4 and 17-hydroxyprogesterone rose in a parallel, phasic manner, an abrupt increase in slope occurred between -6 h and +30 h but an acute rise in P4 was not consistently observed among individuals. The surge onset to follicle rupture interval (mean 37.6 +/- 4.2 h) positively correlated with peak LH-RIA (r = 0.76, P less than 0.05), surge amplitude (r = 0.74, P less than 0.05) and surge onset to peak interval (r = 0.87, P less than 0.02), but not surge duration. There were no significant relationships between E2 or P4 (mean, peak, integrated, slope) and surge amplitude or duration (LH-RIA, FSH), peak value, or surge onset to peak interval (LH-RIA, LH-BIO, FSH). These data suggest that in women, 1) onset of the midcycle surge in LH-RIA and LH-BIO is simultaneous, and 2) surge characteristics are not influenced by physiological variations in steroid hormone secretion that occur beyond the thresholds required for surge initiation.

Adult↗
PubMed1991

Effect of clomiphene citrate treatment on endometrial estrogen and progesterone receptor induction in women.

A direct adverse effect of clomiphene citrate on the endometrium has been presumed, and interference with estrogen receptor-mediated endometrial estrogen receptor and progesterone receptor induction has been implicated as the mechanism responsible for an increased incidence of luteal phase deficiency in association with clomiphene citrate treatment. To clarify the net influence of clomiphene administration on endometrial steroid receptor induction, we studied five normal ovulatory women, in both a spontaneous and clomiphene-induced (150 mg/day, cycle days 5 to 9) ovulatory cycle. From cycle day 11 blood samples were obtained daily and urinary luteinizing hormone determinations were performed twice daily. Endometrial biopsy was performed on the day of the urinary luteinizing hormone surge and again 13 days after the surge. Serum levels of follicle-stimulating hormone and luteinizing hormone were determined by immunoradiometric assay, estradiol and progesterone by radioimmunoassay, and clomiphene citrate isomer concentrations in treatment cycles by reversed-phase high-performance liquid chromatography and fluorescence detection. Total, cytosolic, and salt-extracted nuclear endometrial estrogen receptor and progesterone receptor concentrations were determined by enzyme-linked immunoassay. Serum estradiol was threefold to fivefold higher (p less than 0.05) in clomiphene-induced than in spontaneous cycles 8 and 10 days before the luteinizing hormone surge, and progesterone was increased (p less than 0.05) from the day of the surge to end of the cycle. Serum enclomiphene rose to plateau between 12 and 6 days before the luteinizing hormone surge (4.1 +/- 0.8 ng/ml, mean +/- SE, n = 19) and fell thereafter to less than 1.0 ng/ml. Zuclomiphene levels increased rapidly between 14 and 8 days before the surge (53.9 +/- 2.8 ng/ml, mean +/- SE, n = 5) and then decreased gradually but remained elevated throughout the luteal phase (29.0 +/- 1.2 ng/ml, mean +/- SE, n = 33). Late luteal endometrial histology was abnormal in one of four available treatment cycle specimens, but the endocrine characteristics and number and subcellular distribution of estrogen receptor and progesterone receptor in the abnormal cycle were not different from those of normal, in-phase cycles.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Fetal death associated with a t(1;14) in three generations.

Fetal death is a common phenomenon; parental chromosome study may uncover the cause of the problem and contribute to the management of the couple involved. Discovery of a translocation provides a firm basis for genetic counseling, detection of carriers, and prenatal diagnosis. We have studied a young couple with a history of 4 consecutive spontaneous abortions before cytogenetic study demonstrated the father to carry a t(1;14). The translocation was found in 2 other adults, a liveborn child, and a fetus, in a total of 3 generations.

Abortion, Habitual↗
PubMed1987

Properties of a ribonuclease from Aedes aegypti larvae.

1. The properties of a soluble ribonuclease from Aedes aegypti larvae have been compared with ribonuclease activity in adult female tissue. 2. In larval extracts ribonuclease activity was maximal at 40-45 degrees C whereas activity in tissue from adult females was highest at 50 degrees C. 3. Ribonuclease activity that was recovered in a 20-60% ammonium sulfate precipitate was further purified by batch elution from DEAE-Sephacel and from carboxymethylcellulose. 4. Ribonuclease activity in the partially purified fraction was sensitive to EDTA, stimulated by magnesium, had a pH optimum at 9.0 and a Mr of 45,000. 5. Agarose gels containing yeast RNA substrate were used to monitor partial purification of the larval ribonuclease.

Aedes↗
PubMed1987

The effect of luteal phase estrogen antagonism on endometrial development and luteal function in women.

Previous studies of the role of estrogen in primate luteolysis, designed to investigate the effects of estrogen antagonism or selective inhibition of luteal phase estrogen production on luteal function, have ignored the impact of such treatments on secretory endometrial development. We examined the effect of luteal phase estrogen antagonism on endometrial maturation and luteal function in six women. In each of two menstrual cycles in each woman, blood samples were obtained on alternate days from cycle days 3-9, daily until 1 day after the urinary LH surge (day 0), and again on alternate days until the onset of menses. In the second of each pair of cycles, clomiphene citrate (100 mg) was administered daily from 2 days after the LH surge until menses. Endometrial biopsy was performed 13 days after the LH surge in each cycle. Serum FSH, LH, estradiol, and progesterone (P) were measured by RIA. The endometrial histological date and concentration of cytosolic (C) and nuclear (N) estrogen (ER) and P (PR) receptors were determined. We found significant (P less than 0.05) increases in luteal phase serum FSH, LH, estradiol, and P levels in the clomiphene cycle compared to those in the control cycle. Endometrial histology was significantly (P less than 0.002) different during estrogen antagonism; a maturation delay of more than 2 days was found in all six women during the clomiphene cycle. Luteal phase duration was unchanged by clomiphene (P = 0.29). Endometrial ER-C [7.38 +/- 2.52 (+/- SEM) vs. 38.75 +/- 10.17 fmol/mg protein], ER-N (248 +/- 84 vs. 685 +/- 80 fmol/mg DNA), and PR-C (97 +/- 38 vs. 189 +/- 38 fmol/mg protein) were significantly lower (P less than 0.03) in the clomiphene cycle than in the control cycle, whereas PR-N was not different (P greater than 0.10). These data suggest that luteal phase estrogen 1) modulates endometrial PR and 2) plays an important role in secretory endometrial development.

Adult↗
PubMed1987

Doubling time of human chorionic gonadotropin (hCG) in early normal pregnancy: relationship to hCG concentration and gestational age.

There is controversy regarding whether the doubling time of human chorionic gonadotropin (hCG) in early normal pregnancy is constant or rises with increasing gestational age (GA) and hCG concentration. To clarify the influence of these variables on hCG doubling time, we obtained serial blood specimens every 2 to 4 days between postovulatory day 12 and 70 from 16 women who conceived while monitoring basal body temperature. The serum concentration of beta-hCG was determined by radioimmunoassay. Serial doubling time of hCG was calculated in all subjects and correlated with GA and hCG concentration. Least-squares estimates of 95% confidence bands were established from regression analysis given the second hCG concentration for each pair of samples or GA. For elimination of the need for calculation and thus improvement of the clinical utility of doubling time determinations, a nomogram relating the concentrations of hCG in paired serum samples to doubling time was constructed. We observed a significant correlation of doubling time with hCG concentration and GA, both in the group overall and within each individual pregnancy. These data support the recommendation that doubling time determinations should be evaluated with reference to normal values for a given GA or hCG concentration and suggest that previously proposed normal values of doubling time in early normal pregnancy may be low.

Chorionic Gonadotropin↗
PubMed1986

Maternal estradiol response to alterations in uteroplacental blood flow.

Low levels of maternal estrogens are commonly regarded as indicators of fetal stress. We continuously monitored distal aortic blood flow by flowmeter, fetal heart rate, and amniotic fluid pressure in seven pregnant baboons near term. Four of the animals received a constant intravenous infusion of [7-3H]dehydroepiandrosterone and [4-14C]estradiol for 270 minutes. A 50% reduction in mean distal aortic blood flow was imposed after 60 minutes by means of partial occlusion of the aorta with a snare device and released at 180 minutes. Blood was collected at 10-minute intervals from 30 to 60 minutes, 120 to 180 minutes, and 240 to 270 minutes. Concentrations of dehydroepiandrosterone, dehydroepiandrosterone sulfate, estradiol, and cortisol in maternal plasma were determined by radioimmunoassay. Metabolic clearance rates of dehydroepiandrosterone and estradiol were calculated from plasma concentrations of [3H]dehydroepiandrosterone and [14C]estradiol. There was no significant change in maternal levels of dehydroepiandrosterone, dehydroepiandrosterone sulfate, or cortisol with alterations in distal aortic blood flow. Three animals exhibited no fetal heart rate evidence of fetal stress; estradiol levels declined during occlusion and returned toward control after release of the snare. Four animals exhibited repetitive late decelerations under conditions of reduced flow; estradiol was unchanged or rose slightly during occlusion but increased three- to 10-fold after release whereas the metabolic clearance rate of both dehydroepiandrosterone and estradiol remained stable. We conclude that placental hypoperfusion without fetal stress results in decreased conversion of aromatizable substrate and elevated maternal estradiol levels during acute hypoxemic fetal stress probably represent increased production of fetal androgen.

Animals↗
PubMed1986

Changes in ribonuclease activity during development of the mosquito, Aedes aegypti.

In the mosquito Aedes aegypti, quantitative and qualitative changes have been detected in ribonuclease activity during development. Ribonuclease activity is particularly high in extracts from larvae, relative to that in extracts from pupae or adults. Larval extract is enriched for a ribonuclease that is heat-labile, has an alkaline pH optimum, and is extremely sensitive to the divalent cation, manganese. Extract from adult females is enriched for a heat-stable component that has an acidic pH optimum and is more active at 56 than at 30 degrees C. Throughout the vitellogenic cycle, no major changes in ribonuclease activity were detected in fat body extracts.

Aedes↗
PubMed1985

Relationship of uteroplacental blood flow to placental clearance of maternal plasma C-19 steroids: evaluation of mathematical models.

The concept that the placental clearance of maternal plasma dehydroepiandrosterone sulfate through estradiol formation is a function of uteroplacental blood flow in women has been disputed. We obtained data on the clearance of maternal plasma dehydroepiandrosterone through placental estradiol formation in the baboon and used these data to evaluate some mathematical models of placental clearance. Our evaluation shows that the placental clearance of dehydroepiandrosterone is proportional to uteroplacental blood flow in the baboon.

Animals↗
PubMed1985

Direct effect of sex steroid-binding protein (SBP) of plasma on the metabolic clearance rate of testosterone in the rhesus macaque.

We report direct evidence for the effect of the sex steroid-binding protein (SBP) on the metabolic clearance rate of testosterone (MCRT). Pure rhesus SBP or human SBP was infused intravenously into three different cycling female rhesus monkeys. MCRT was measured before and after SBP had reached 150-300% of basal levels. A decrease in MCRT was observed in all cases. The effect of SBP on MCRT was tested further in four additional cycling females by infusing immunoaffinity-purified monospecific human SBP antibodies known to cross-react with rhesus SBP. SBP dropped to 54, 40, 4 and 2% of basal levels with a concomitant increase of 118, 190, 320 and 640% of basal MCRT. In one of these animals, pure rabbit SBP was administered after the anti-human SBP infusion resulting in a decrease in MCRT. The magnitude of the SBP effect on MCRT is related to the distribution of testosterone (T) bound to SBP and albumin in the plasma. Calculations show that as long as the percent of T bound to SBP is equal or higher than the percent of T bound to albumin, the influence on MCRT is small. However, if SBP is reduced to the extent that T is bound mostly to albumin, the redistribution of T is associated with a dramatic increase in MCRT. We conclude that under normal conditions each animal has an optimum concentration of plasma SBP which binds a maximum amount of T. If SBP increases above this level, little effect on MCRT will result. However, a drop below the optimum level, as is the case in certain physiological or clinical conditions, will produce a large increase in the clearance of T.

Animals↗