Search PubMed⌕ Search

Biomedical subjects

R J Chang

Publications and source records attributed to R J Chang.

105 records · Page 6Linked to original sources

Progesterone effects on gonadotropin release in women pretreated with estradiol.

This study was designed to investigate whether the amounts of progesterone (P) normally present at midcycle, when administered to normal women pretreated with estradiol benzoate (E2B), alter the release of LH and FSH. Twelve subjects (four groups of three) were studied during two menstrual cycles. On day 1 of both the initial (E2 control) and a subsequent (study) cycle, each subject received E2B im (2.5 micrograms/kg/12 h) for a total of seven injections. Twelve hours after the final injection, gonadotropin-releasing hormone (GnRH) was given. In the study cycle, P in oil was added to each of the last three injections of E2B in doses of 1.25 (group I), 2.5 (group II), or 5.0 (group III) mg/12 h, and in one group (IV) in graded doses of 1.25 2.5, and 5.0 mg/12 h. Estradiol levels were similar in both cycles, with a mean (+/- SE) of 271 +/- 3 pg/ml. During the interval of P administration, mean P levels rose gradually from 0.3 +/- 0.02 to 1.3 +/-0.12 ng/ml (mean +/- SE of all groups). In the study cycle, an FSH rise occurred in 8 of 12 subjects, while an LH surge greater than that in the E2 control cycle occurred in all but one subject. Peak levels of these surges usually occurred within 24 h of the initial P injection, which is similar to the relationship between the initial rise of P and the occurrence of peak gonadotropin levels at midcycle in normal women. The mean delta max of FSH and LH in subjects exhibiting gonadotropin rises approximated the magnitude of the gonadotropin increases observed normally at midcycle. In response to GnRH during the study cycle, the magnitude of the FSH rise was augmented in 6 of 12 subjects and of LH in 9 of 12, when compared to the E2 control cycles. These data suggest that P, in the presence of late follicular phase levels of E2, 1) augments the release of LH, 2) may induce the release of FSH, and 3) further modulates pituitary responsiveness to GnRH. The data are consistent with the hypothesis that the rising concentrations of E2 to which the hypothalamic-pituitary system is exposed for an appropriate duration serve to initiate the surge of LH at midcycle. This increased LH in turn, stimulates the production of P, which not only further augments the LH surge but, when coupled with E2, also can effect the midcycle FSH surge.

Estradiol↗

Protracted circulating lifetimes of mannose-terminated glycoproteins and aggregated albumin in mice infected with LDH-elevating virus.

Several macromolecular homeostasis-regulating mechanisms were tested for functional integrities in mice during acute and early chronic phases of infection with lactic dehydrogenase-elevating virus (LDV). Fractional catabolic rates of carbodiimide-aggregated albumin and immunoglobulin G were studied to evaluate glomerular filtration and hepatic Kupffer cell phagocytic activities. Several glycoproteins (fetuin, IgG antibodies, and ovalbumin) were also compared with their deglycosylated counterparts for fractional catabolic rates and organ distributions as a basis for evaluating virus-induced modifications of saccharide-binding "receptor functions" in vivo. Findings were that normal hepatic clearance of aggregated albumin and of ovalbumin is slowed from the onset of viremia. Fractional catabolic rates of amannosyl-ovalbumin and amannosyl-IgG are similar in uninfected animals to those seen with native ovalbumin or with mannose-terminated IgG in LDV-infected animals. Ovalbumin and aggregated albumin were also found to be mutually competitive for hepatic uptake in uninfected animals. It is proposed that LDV, which replicates in cells of the mononuclear phagocyte system (reticuloendothelial system), alters the clearance functional state of fixed tissue macrophage, thereby explaining in part the protracted circulatory longevity of several enzymes, aggregated albumin and mannose-terminated ovalbumin, and IgG in LDV-infected mice.

Animals↗

Detection, evaluation, and treatment of pituitary microadenomas in patients with galactorrhea and amenorrhea.

Over a period of two and a half years, 34 women with galactorrhea or amenorrhea, all with an abnormal sellar polytomogram, underwent transsphenoidal microsurgical exploration of the sella. Eighteen women and microadenomas (less than or equal to 1 cm. in diameter), seven had macroadenomas (greater than than 1 cm. in diameter), and five had unidentified lesions. Only one women had a normal pituitary gland. Three women had cryosurgery without biopsy. Preoperatively, hyperprolactinemia occurred in 24 of 25 women with adenomas and two of five with nonadenomatous lesions. There were no operative deaths. Significant morbidity occurred in only three patients, none of whom had microadenomas. Postoperatively, menses resumed in 16 of the 17 women with microadenomas and in two of the seven with macroadenomas who presented with amenorrhea. Galactorrhea disappeared in 15 of the 17 women with microadenomas and in four of the seven with macroadenomas who presented with galactorrhea. In five patients with unidentified lesions, a return of menses occurred in two of four with previous amenorrhea, and galactorrhea abated in two of three who presented with lactation. We conclude that sellar polytomography in women with hyperprolactinemia is a useful technique technique for the diagnosis of pituitary adenomas, a lesion which may occur more frequently than previously realized. In addition, transsphenoidal microresection of microadenomas is safe and effective.

Adenoma↗

Serum progesterone and estradiol-17beta levels in premature and term labor.

A total of 30 to 50 per cent of premature labors occur without identifiable predisposing conditions. To evaluate the hormonal status of these pregnancies, serum progesterone (P) and estradiol (E2) were measured by radioimmunoassay singly in 60 premature labor patients and serially in 19 normal pregnancies. Premature labor patients as a group have significantly lower P and E2 levels than controls. Pregnancies complcated by idiopathic premature labor (IPL) (p less than 0.01), premature labor secondary to abruptio-marginal separation (A-MS) (p less than 0.05), and premature rupture of membranes (PROM) (p less than 0.05) have significantly lower P levels than controls. Patients with IPL and A-MS have significantly lower P levels (p less than 0.01) than PROM patients. No significant change in P or E2 occurs immediately prior to normal term labor. Conclusions are that (1) premature labor patients have significantly lower Pand E2 levels than controls, (2) the degree of P depression varies according to the type of premature labor and (3) IPL is characterized by premature labor with no identifiable predisposing factors.

Estradiol↗

Effect of dexamethasone and clomiphene citrate on peripheral steroid levels and ovarian function in a hirsute amenorrheic patient.

A 22-year-old infertile woman with amenorrhea and mild hirsutism failed to experience uterine bleeding following withdrawal of progestin therapy and failed to ovulate or menstruate following treatment with clomiphene citrate in doses up to 200 mg/day for 5 days. Clomiphene citrate, 200 mg/day, plus 10,000 IU of human chorionic gonadotropin given on day 13 also failed to induce either ovulation or menses. Serum androgen levels were: cortisol, 186 ng/ml; dehydroepiandrosterone sulfate, 6400 ng/ml; dehydroepiandrosterone, 17.92 ng/ml; androstenedione, 4.68 ng/ml; testosterone, 1.28 ng/ml; and dihydrotestosterone, 0.75 ng/ml. Upper limits of normal values for these androgens in our laboratory are, respectively: 140, 2500, 8.0, 2.3, 0.5, and 0.35 ng/ml. The dexamethasone (Dex) suppression test indicated predominantly an adrenal source of the hyperandrogenism. Except for androstenedione the levels of all androgens measured returned to normal following treatment with 0.5 mg of Dex/day. Four months of this treatment had a beneficial effect on the hirsutism but failed to induce ovulation or menses. Clomiphene citrate, 100 mg/day for 5 days, given concurrently with Dex therapy resulted in ovulation and conception. Adrenal androgen excess has been postulated to be a cause of ovarian dysfunction. Our data support this postulate.

Adult↗

Simultaneous comparison of delta 5-3beta-hydroxysteroid levels in the fetoplacental circulation of normal pregnancy in labor and not in labor.

Concentrations of pregnenolone (delta5P), dehydroepiandrosterone (DHEA), 16alpha-hydroxydehydroepiandrosterone (16alpha-OH DHEA), pregnenolone sulfate (delta5P-S), and dehydroepiandrosterone sulfate (DHEA-S) were measured simultaneously by radioimmunoassay in individual, paired umbilical artery (UA) and vein (UV) sera from 18 normal term pregnancies, 6 in labor, 12 not in labor. Mean UA and UV levels +/- SEM (ng/ml) were for delta5P: 30.39 +/- 1.69, 35.55 +/- 3.06; DHEA: 12.31 +/- 2.34, 3.66 +/- 0.38; 16alpha-OH DHEA: 7.48 +/- 0.63, 10.59 +/- 0.78; delta5P-S: 1,652 +/- 154, 1,486 +/- 130; DHEA-S: 2,122 +/- 134, +/- 134, 1,906 +/- 134. Umbilical artery delta5P-S, DHEA-S, and DHEA levels were significantly higher than UV levels, whereas the reverse was true for delta5P and 16alpha-OH DHEA. The inverse arterio-venous (A-V) gradient for 16alpha-OH DHEA was contrary to previous published reports using pooled samples. Comparison by linear regression of paired UA and UV steroid concentrations of delta5P, delta5P-S, DHEA, and DHEA-S revealed a significant correlation (P less than 0.01) for each steroid. Labor was associated with a significant increase in UA levels of DHEA-S and a smaller, but not quite significant, increase in UA levels of delta5P-S, while similar changes for unconjugated delta5-3beta-hydroxysteroids were not observed. Mean A-V gradients between the group of patients in labor and those not in labor were not significantly different. These data demonstrate that: 1) a significant difference between UA and UV concentrations exists for delta5P, DHEA, 16alpha-OH DHEA, delta5P-S, and DHEA-S; 2) there is a significant correlation between UA and UV concentrations for delta5P, DHEA, delta5P-S, and DHEA-S, implying that each fetoplacental unit maintains an equilibrium relative to these steroid concentrations in the umbilical circulation; 3) labor is associated with a significant increase in UA levels of DHEA-S and probably of delta5P-S.

Blood↗

Effect of dexamethasone on serum cortisol and androgen levels in hirsute patients.

The serum levels of the following steroids were measured in 59 hirsute patients before (control) and after (post-dexamethasone) administration of dexamethasone (Dex) for 7 days: cortisol (F), dehydroepiandrosterone (DHEA), its sulfate (DHEA-S), androstenedione (A), testosterone (T), and 5alpha-dihydrotestosterone (DHT). Assuming that Dex-suppressibility implied adrenal origin, the source of excess androgens was also evaluated. All patients showed elevated level of only one androgen: 4 had elevated DHEA-S; 4 had elevated T; 3 had elevated DHT. No patient had an elevated DHEA or A without an evelation of the other androgens. The control levels of DHEA-S were above normal in 45 patients; the DHT levels were elevated in 43 patients; 31 patients had elevated T levels; and 25 patients elevated A; and 24 patients, DHEA levels. In 32 patients with adequate suppression of adrenal androgens after 7 days of Dex administration, the source of excess androgens could be evaluated. Of 13 patients with elevated A levls, the excess A production was of adrenal origin in 6 cases, of ovarian origin in 5 cases, and of mixed origin in 2 cases. Of 15 patients with elevated T levels, the excess T production was of adrenal origin in 3 cases, of ovarian origin in 10 cases, and of mixed origin in the remaining 2 cases. Of 25 patients with elevated DHT levels, the excess DHT production was of adrenal origin in 16 patients, of ovarian origin in 5 patients, and of mixed origin in 4 patients. Of the 32 patients with an adequate Dex suppression test, 14 showed evidence of adrenal hyperandrogenism, 5 had ovarian hyperandrogenism, and mixed hyperandrogenism was present in the remaining 13 patients. There was an adrenal source of hyperandrogenism in 27 of 32 patients (14 pure adrenal and 13 mixed adrenal-ovarian), which represents 85% of the 32 patients.

Adolescent↗

Peripheral steroid levels in a patient with congenital absence of the uterus.

In a patient with congenital absence of the uterus, daily measurements of progesterone (P), 17-hydroxyprogesterone (17-P), pregnenolone (delta5P), 17-hydroxypregnenolone (17-delta5P), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), testosterone (T), dihydrotestosterone (DHT), androstenedione (A), estrone (E1), estradiol-17beta (E2), and cortisol (F) were performed over a period of 48 consecutive days. Serum P, 17-P, and E2 determinations revealed normal, cyclical ovarian activity consisting of two luteal phases and one follicular phase. Serum E1, delta5P, and DHEA-S levels were normal throughout the study, whereas DHEA and DHT levels were persistently elevated. Serum levels of 17-delta5P and A showed peak levels above normal. Serum T and F concentrations were normal during the initial part of the study, but some elevation was seen during the second luteal phase. In the patient studied, absence of the uterus did not seem to interfere with cyclic ovarian activity. The role of the uterus in the metabolism of androgens remains subject to further investigation.

17-alpha-Hydroxypregnenolone↗

Peripheral arterial and venous concentrations of various androgens in patients with and without hirsutism.

The mean peripheral arteriovenous difference for dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), androstenedione (A), testosterone (T), 5ALPHA-dihydrotestosterone (DHT), and 17-hydroxyprogesterone (17-P) has been calculated in 7 nonhirsute and 9 hirsute women. No significant difference was found between peripheral artery and vein concentrations for all steroids measured in both groups of women studied. Since steroid concentrations in peripheral arterial samples are not expected to differ from those from ovarian and adrenal arteries, it is concluded that peripheral venous steroid levels adequately represent the steroid concentrations of arterial blood delivered to steroid-producing tissue.

Androgens↗

The relationship between the motility and morphology of spermatozoa in human semen.

High-speed videomicrography was used to assess simultaneously the morphology and motility of seminal spermatozoa from 10 fertile donors and 10 patients being evaluated for infertility. In both donors and patients, morphologically normal spermatozoa were more likely to be motile and had significantly higher straight line velocity, greater rolling frequency and flagellar beat frequency than abnormally shaped cells. For donors and patients there were highly significant, linear correlations (R = 0.7 to R = 0.98) between the movement characteristics of morphologically normal and abnormal spermatozoa within an ejaculate. A greater percentage of normal donor spermatozoa were motile than were the normal spermatozoa from patients (56% vs. 28%, respectively, P less than 0.005) and normal donor spermatozoa also swam faster than normal patient spermatozoa (49.1 +/- 3.2 microns/sec vs. 37.4 +/- 4.3 microns/sec, mean +/- sem, respectively, P less than 0.05). Overall, a multivariate analysis of variance, including straight line velocity, rolling frequency, beat frequency, and flagellar beat amplitude, demonstrated that these movement characteristics were significantly greater for the normal cells from donors than for the normal spermatozoa from patients. These biologic distinctions notwithstanding, the discrimination between semen from donors and patients was not improved when only morphologically normal cells were analyzed for motility.

Humans↗