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Biomedical subjects

D T MacLaughlin

Publications and source records attributed to D T MacLaughlin.

67 records · Page 4Linked to original sources
PubMed1983

Specific estradiol binding in embryonic Mullerian ducts: a potential modulator of regression in the male and female chick.

The total content of putative estradiol-specific cytosolic type I and nuclear type I and II estradiol-specific binders was measured in 8- and 9-day-old male and female chick embryo Mullerian ducts. Cytosolic and nuclear type I estradiol-specific binding levels were similar in males and females, and no significant differences were noted among right vs. left and 8-day-old vs. 9-day-old embryo Mullerian ducts. The levels of nuclear type I estradiol binder were consistently higher than the cytosolic type I binder, but this difference was not significant. Nuclear type II estradiol-specific binding, however, was significantly higher in the left Mullerian ducts of both male and female embryos. The significance of these findings in relation to the regression of Mullerian ducts in male and female chick embryos is discussed.

Animals↗
PubMed1982

Steroid enhancement of Mullerian duct regression.

The biologic activity of the glycoprotein, Mullerian Inhibiting Substance (MIS), was enhanced by added testosterone, medroxyprogesterone acetate, and progesterone, although these steroids did not cause Mullerian duct regression when added alone. Statistically significant augmentation by testosterone and medroxyprogesterone was observed at concentrations of 10(-7) and 10(-8) M. Progesterone enhanced MIS activity at a concentration of 10(-6) M. By contrast, dihydrotestosterone, estradiol, and corticosterone at concentrations of 10(-9) to 10(-5) M produced no significant effect on MIS activity. Since MIS does not bind directly to the steroids studied, we suspect that the enhancement effect occurs at the receptor level, probably at the mesenchyme as observed in other developmental systems.

Animals↗
PubMed1982

Uveal melanomas presenting during pregnancy and the investigation of oestrogen receptors in melanomas.

We observed a young woman who showed growth of a choroidal melanoma over the course of 2 pregnancies, with subsequent enucleation of the eye. This is the first such documented case. In addition 4 other women with uveal malignant melanomas presented during pregnancy. This observed number of pregnancies (5) was greater than the expected number (2.1) among women of childbearing age who underwent enucleation with subsequent analysis in our pathology laboratory. However, this difference was not statistically significant. Further, more females 44 years of age or younger underwent enucleation for malignant melanoma than men of comparable age. Evaluation of these cases led us to propose that there is a subset of patients whose ocular melanomas are hormonally responsive. We therefore analysed uveal melanoma and choroidal tissue from 7 patients, including one of the pregnant women, for the presence of oestrogen receptors. No specific oestrogen binding was found. The possibilities that other hormones are involved or an immunological mechanism is operative are discussed.

Adult↗
PubMed1981

Specific estradiol binding in schwannomas, meningiomas, and neurofibromas.

The cytoplasmic fractions of schwannomas (acoustic neuromas), meningiomas, and neurofibromas were assayed for the presence of estrogen receptors. Specific estradiol binding was detected in 7 of 16 schwannomas, 7 of 10 meningiomas, and 1 of 6 neurofibromas. A nontumorous vestibular nerve was also studied and showed no estradiol binding. In the tumors, the concentration of the estradiol binding sites as estimated by saturation binding analysis covered a wide range of values (21 to 2430 fmol/g of tumor) but, overall, meningiomas contained the highest amount of estradiol binder. A Scatchard plot analysis of one of the schwannoma specimens demonstrated high affinity estradiol binding (Ka = 1.695 X 10(10) M-1). Although there were more females than males in each tumor category, the overall incidence of estradiol binding was similar in males (5 of 11, 45%) and in females (10 of 21, 48%). In 5 cases, progestin binding was also measured and was detected in two meningiomas (both from female patients); one meningioma and two neurofibromas showed no progestin binding. A discussion is presented of the possible role of estradiol in the pathogenesis or modulation of meningeal and Schwann cell tumors as well as in the genetic disorder neurofibromatosis.

Adolescent↗
PubMed1977

Ultrastructure of human endometrial epithelium in monolayer culture with and without steroid hormones.

Colonies of cells of epithelioid appearance were identified in monolayer cultures grown up to 50 days from normal human endometrial cell suspension obtained by a method designed to insure a maximum harvest of glandular cells. Groups of these cells were separated from stromal cells by means of cloning cylinders. Studies comparing the ultrastructure of cells of this type to fresh endometrial tissue revealed a number of similarities. The morphological characteristics common to both types of samples included junctional complexes, perinuclear microfilaments and microvilli with glycocalyx. Other common features were prominent nucleoli, well developed Golgi, rough endoplasmic reticulum and membrane-bound electron-dense bodies in the cytoplasm. A stripping technique applied to the fetal bovine serum used in the nutrient medium made it possible to initiate cultures in a steroid-free environment and to maintain them in the presence of the specified concentration of estradiol and/or progesterone. Isolation of epithelial cells of endometrium in monolayer culture may provide a useful model system in which to study the specific effects of steroid hormones on cellular function and differentiation.

Culture Techniques↗
PubMed1976

Progesterone binding by normal and abnormal human endometrium.

Cytosols from 75 normal, 36 abnormal, and 5 decidual human endometrial tissue specimens were assayed for the presence of a high affinity, progesterone-specific binding protein. Thirty of the normal and 15 of the abnormal samples were found to contain a binder which would form a high-affinity complex with progesterone but not with cortisol, 17beta-estradiol, testosterone, or 5alpha-androstane-3-,17-dione. Incubation of cytosol with trypsin or incubation for 2 hours at 37 C abolished [3H]progesterone binding by these preparations, indicating the protein nature and heat-lability of the binder. The average equilibrium constant of dissociation, Kd, of the progesterone-binder complex was 4.0 X 10(-10)M in each phase of the menstrual cycle. The concentration of the binder varied over the cycle, however, with a significant peak at mid-cycle (P = .02). The average saturation values in femtomoles (fmoles)/mg protein ranged from 21 in the early proliferative phase to 64 in the late proliferative samples, dropping to 36 in early secretory and to 3 in the late secretory phase of the cycle. No progesterone-specific binding was detected in decidual samples. Saturable binding was demonstrable in 10 of 22 endometrial hyperplasias, 80-1840 fmoles/mg protein, with high affinity, Kd 3.3 X 10(-10)M. Two other hyperplasia samples bound progesterone, but with lower affinity. Two grade I adenocarcinomas, one grade III adenosquamous carcinoma, and one grade III adenocarcinoma contained the progesterone binder, but in 9 other cancers no detectable binder was present. A benigh adenocanthomyoma was found to contain a progesterone binder (18 fmoles/mg protein with a Kd of 2.5 X 10(-10)M).

Adenocarcinoma↗
PubMedDate not supplied

Interlaboratory interprotocol comparison of indirect immunobead assay for sperm-associated antibodies in serum.

This investigation was designed to study the effect of two different protocols on the indirect sperm-associated antibody test on serum performed using Bio-Rad immunobead (IBT) at two andrology laboratories. Aliquots of 31 serum samples from infertile couples were analyzed by both protocols. The IBT was negative by both protocols (100% concordance) for 18 serum samples. Seven of the 13 remaining samples were positive by both protocols (> or = 10% bead attachment by protocol A and > or = 20% bead attachment by protocol B), for a concordance of 54%. The remaining six samples were positive by one of the two protocols. The overall concordance for positive and negative results was 81% (25 of 31 samples). Protocol A detected a higher percentage of bead attachments for IgG and IgA, while protocol B detected a higher percentage of bead attachments for IgM. The discordance in the results of IgA attachment obtained by the two protocols was statistically significant (p < .05). A standardized, uniform protocol for the indirect IBT is needed.

Autoantibodies↗
PubMedDate not supplied

Müllerian inhibiting substance inhibits testosterone synthesis in adult rats.

Müllerian inhibiting substance (MIS) is a gonadal hormone that causes regression of the Müllerian ducts during male sexual differentiation. Postnatally, MIS inhibits the proliferation and differentiation of immature Leydig cells, and transgenic mice that overexpress MIS have decreased serum testosterone concentrations. To elucidate the effects of MIS on androgen regulation in the postnatal testis, we examined testosterone synthesis in adult Sprague-Dawley rats following intratesticular and intraperitoneal injections of MIS. Intratesticular MIS injection achieved high local concentrations of MIS (574.0 +/- 60.0 ng/mL) at 4 hours, with a corresponding decline in serum testosterone concentrations to 0.7 +/- 0.1 ng/mL, compared to 1.1 +/- 0.2 ng/mL with intraperitoneal MIS and 1.6 +/- 0.1 ng/mL with intratesticular vehicle (IT-Veh) (P < .001). Intratesticular administration of MIS (IT-MIS) resulted in much higher serum and testicular interstitial fluid MIS concentrations than the intraperitoneal route. To directly examine the testosterone production rate in MIS-treated animals, we isolated Leydig cells from MIS and vehicle-injected testes. Primary Leydig cells exposed to MIS had a lower testosterone production rate and decreased expression of p450c17 (hydroxylase/lyase) and luteinizing hormone (LH) receptor mRNAs than that of vehicle-injected controls or the noninjected contralateral testis. In conclusion, intratesticular administration of MIS caused a decline in serum testosterone concentrations by decreasing the rate of testosterone biosynthesis, confirming that MIS can regulate adult Leydig cell androgen production. The ability of MIS to down-regulate mRNA expression of the p450c17 and LH receptor genes suggests that this effect is mediated transcriptionally. These data indicate that, in addition to its role in embryonic differentiation of the male reproductive tract, MIS has a regulatory function in the postnatal testis. We conclude that one such function is for MIS to directly inhibit adult Leydig cell steroidogenesis.

Animals↗