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C J Grossman

Publications and source records attributed to C J Grossman.

49 records · Page 3Linked to original sources
PubMed1984

Analysis and properties of the cytosolic estrogen receptor from rat thymus.

The equilibrium association constant, KA, and the number of receptor binding sites, Bmax, that characterize the estrogen receptor present in rat thymus were determined using five different methods of data analysis on binding data obtained using a dextran-coated-charcoal assay. The methods of data analysis consisted of fitting the binding data directly to the hyperbolic binding function, fitting the data to the Lineweaver-Burk, Scatchard, and Woolf transforms of the hyperbolic function, and the direct linear plot method of Eisenthal--Cornish-Bowden. The Woolf and Eisenthal--Cornish-Bowden methods gave identical results indicating that added estradiol caused a decrease in KA (competitive inhibition) and a marked decrease in Bmax (noncompetitive inhibition). The Scatchard analyses gave only a very qualitative indication of this trend, while the Lineweaver-Burk analyses gave no indication of any such systematic trend. The results from the computationally more difficult fits to the hyperbolic binding equation were in agreement with the Woolf and Eisenthal--Cornish-Bowden results. Thus, the cytosolic thymus estrogen receptor from the rat shows both competitive and noncompetitive inhibition in the presence of endogenous or exogenous estradiol.

Analysis of Variance↗
PubMed1983

The interrelationship of the HPG-thymic axis and immune system regulation.

It is well established that gonadal steroids play an important role in the regulation of immune response. These substances exert their effect through estradiol and possibly dihydrotestosterone receptors located in the thymic reticuloepithelial cell matrix. In vivo treatment of male rats with estradiol has been shown to depress the cell mediated immune response as mediated through thymic serum factors. Castration stimulates the cell mediated immune response while thymectomy inhibits this effect. It also appears that growth hormone at physiological concentrations can directly inhibit thymocyte blast transformation in vitro while leutinizing hormone, follicle stimulating hormone, and prolactin do not directly affect thymocyte function. A tentative scheme for immune system regulation by the HPG-thymic axis is presented.

Animals↗
PubMed1983

Dihydrotestosterone regulation of thymocyte function in the rat mediation by serum factors.

We have previously reported that reticuloepithelial cells of rat thymic tissue contain specific, high-affinity estrogen (E) and dihydrotestosterone (DHT) receptors which are not present in thymocytes, and that stimulation of the concanavalin A (Con A) sensitive thymocyte population is by means of a thymic serum substance depressed by estradiol. To ascertain if a serum substance modulated by DHT could also effect a thymocyte population, we incubated thymocytes in vitro for 3 days in the presence of the mitogens Con A or phytohaemagglutinin (PHA) + tissue culture media + 20% specific rat serum preparations and pulse labelled with tritiated thymidine. Rat serum samples were prepared from control, castrate, thymectomized (Tx) and castrate-Tx animals as well as from similar groups of animals treated in vitro for 3 days with physiological doses of DHT. It was found that there was a significant enhancement of thymocyte blastogenesis in cultures incubated with castrate rat serum + Con A or PHA vs control serum cultures (P less than 0.001). Direct replacement of DHT either to normal or castrate sera in vitro at physiological concentrations did not alter the level of thymocyte blastogenesis from normal or castrate controls. Sera prepared from castrate animals treated with DHT at physiological concentrations did not depress the blastogenic response, but sera from animals treated with testosterone were successful in depressing the blastogenic response to noncastrate levels. Sera prepared from Tx animals were stimulatory on thymocyte blastogenesis when PHA were utilized (P less than 0.02) and this stimulation was depressed in sera from animals treated in vivo with DHT. Sera prepared from Tx or castrate-Tx animals were not able to stimulate thymocyte blastogenesis when Con A was utilized but were stimulatory when prepared from castrate-Tx animals pretreated in vivo with DHT. It is hypothesized that Con A sensitive thymocytes are depressed by a thymic serum factor under the control of E and that both Con A and PHA sensitive thymocytes are depressed by a serum factor possibly of extrathymic origin that is under the control of DHT. A tentative hypothesis for the regulation of thymocytes by gonadal steroid hormones is presented.

Animals↗
PubMed1983

Characteristics of the cytoplasmic and nuclear dihydrotestosterone receptors of human thymic tissue.

Dihydrotestosterone receptor was prepared from both the cytoplasm and nucleus of human thymic tissue. Human cytoplasmic and nuclear dihydrotestosterone receptor possessed a KA greater than 1.0 and by competition assay was highly specific for dihydrotestosterone. Human thymic cytoplasmic dihydrotestosterone receptor prepared in standard buffer sedimented on 5-20% sucrose gradients in the 4s region but human thymic cytoplasmic dihydrotestosterone receptor prepared in buffer containing sodium molybdate (10 mM) sedimented in the 7s region on 5-20% sucrose gradients. It is concluded that the human thymic dihydrotestosterone receptor is similar to classic androgen receptor.

Adolescent↗
PubMed1982

Estradiol regulation of thymic lymphocyte function in the rat: mediation by serum thymic factors.

Estradiol (E2) can depress the function of the thymic lymphocytes. To determine if this response to a gonadal steroid is regulated directly or indirectly, thymic lymphocytes were incubated in vitro for 3 days in the presence of the mitogens concanavalin A (Con A) or phytohaemagglutinin (PHA) + tissue culture media + 20% specific rat serum fractions and pulse labelled with tritiated thymidine. Rat serum fractions were prepared from control, castrate, thymectomized (Tx) and castrate-Tx animals as well as from similar groups of animals treated in vivo for three days with physiological doses of E2. It was found that there was a significant enhancement of thymocyte blastogenesis in cultures incubated with castrate rat serum + Con A or PHA vs. control serum cultures (P less than 0.001). Direct replacement of E2 to castrate sera in vitro at physiological concentrations failed to depress thymocyte blastogenesis to noncastrate levels. Sera prepared from castrate animals treated with E2 at physiological concentrations was successful in depressing the blastogenic response to noncastrate levels. Sera from Tx animals did not enhance Con A induced blastogenesis, but PHA response was significantly increased (P less than 0.01) This effect was lost utilizing sera from Tx animals treated with E2. It is concluded that thymocyte function is regulated by serum factors which have their origin in the thymus, and that these factors are modulated by a gonadal steroid estradiol.

Adrenalectomy↗
PubMed1979

Rat thymic dihydrotestosterone receptor: preparation, location and physiochemical properties.

Castration in the male rat has been shown to produce enlargement of the thymus gland while treatment with dihydrotestosterone (DHT) results in a decrease in thymic size in these animals. To determine if these changes might be receptor mediated, thymus tissue from castrate male rats was removed and homogenized in buffer and centrifuged to produce cytosol. By Scatchard plot analysis, it was shown that a specific DHT receptor was present at a concentration of 0.24 +/- 0.02 pmoles/g tissue and it possessed a KA of 2.51 +/- 0.45 x 10(9)M-1. This thymic DHT receptor sedimented on 5--20% sucrose gradients in the 8s region. By competition analysis it was found that testosterone only partially competed (25%) for this receptor, with virtually no binding noted for estradiol, progesterone, and cortisol. The receptor was found to be localized in the reticuloepithelial matrix of the thymus and was not present in the thymic lymphocyte fraction.

Animals↗
PubMed1974

Characterization of binding components for progesterone and 5alpha-pregnane-3,20-dione in the hamster uterus.

In the hamster uterus, a specific progesterone (pregn-4-ene-3,20-dione) receptor has been identified in the cytosol fraction. In the present study, we examined hamster uterine cytosol for the possible existence of specific macromolecules that bind the progesterone metabolite, 5alpha-pregnane-3,20-dione. When cytosol was analyzed by density-gradient centrifugation with sucrose-glycerol gradients and by Scatchard plot analysis of [(3)H]5alpha-pregnane-3,20-dione binding data, there was no evidence of specific binding components for this metabolite. In vivo treatment of proestrous hamsters with unlabeled progesterone, 5alpha-pregnane-3,20-dione, or cortisol for 1 hr revealed that only progesterone caused the depletion of progesterone-receptor sites from the uterine cytosol fraction. Incubation of uterine strips which had been preloaded with two different concentrations of [(3)H]-progesterone demonstrated that progesterone was metabolized to 5alpha-pregnane-3,20-dione and to a greater extent to 3alpha-hydroxy-5alpha-pregnan-20-one. The accumulation of 5alpha-pregnane-3,20-dione during progesterone metabolism appeared to be related to the availability of nonspecifically bound hormone. These studies (i) strongly suggest there is no specific receptor system for 5alpha-pregnane-3,20-dione in the uterine cytosol fraction, (ii) confirm the existence of a specific progesterone receptor in uterine cytosol, and (iii) provide evidence that progesterone itself mediates the uterine progestational response via interaction with a specific receptor system.

Animals↗
PubMedDate not supplied

Biphasic in vivo immune function after low- versus high-dose alcohol consumption.

A series of experiments was performed to assess the alterations in immune status in vivo that are associated with differences in the amount and duration of ethanol intake. Using a nonspecific delayed cutaneous hypersensitivity-like response to the intradermal injection of phytohemagglutinin, the area of induration (skin test response) was significantly enhanced (p = 0.008) after low-dose ethanol (0.5 g/kg) administered daily by gastric gavage for 5 days. High-dose ethanol (6.0 g/kg) significantly diminished this response (p = 0.03). Using an experimental model of Mycobacterium bovis hepatitis, the host immune response was also altered in a biphasic manner after chronic, 28-day ethanol consumption. With this model 0.43 +/- 0.03 g/kg/day (mean +/- SEM) of ethanol (low dose) was associated with a 40% improvement in the removal of the organisms from liver tissue (p = 0.002). High dose (12.1 +/- 0.5 g/kg/day) impaired removal, resulting in a 55% increase in the number of viable organisms (p = 0.001). The levels of three cytokines, MIF, TNF-alpha, and IL-2, known to be involved in the modulation of the host response to mycobacterial infections, were measured in sera after the infection. The serum levels of these cytokines in response to infection did not correlate with this biphasic response to different alcohol dose levels.

Animals↗