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Biomedical subjects

S D Michael

Publications and source records attributed to S D Michael.

At least 37 records · Page 2Linked to original sources
PubMed1988

Rapid induction of ovarian granulosa cell tumors by 7,12-dimethylbenz(a)anthracene in neonatally estrogenized mice.

Groups of female C3H/HeMs x 129/J F1 mice were given injections of either 20 micrograms of 17 beta-estradiol or sesame oil (vehicle) for the first 5 days after birth. Half of each group was then given gastric intubations of 20 mg/kg of 7,12-dimethylbenz(a)anthracene (DMBA) at 70, 77, and 84 days of age. The other half of each group was given sesame oil. Thus, this design yielded four experimental groups: oil + oil; 17 beta-estradiol + oil; oil + DMBA; and 17 beta-estradiol + DMBA. They were sacrificed at approximately 144 days of age (Experiment 1) or the day of palpable ovarian tumor detection or 360 days of age (Experiment 2). In Experiment 1, the total number of oocytes (follicles) per ovary in mice of the 17 beta-estradiol + oil group was maintained at the same level as mice of the oil + oil group. A significant reduction of oocytes, however, was observed in mice of the 17 beta-estradiol + DMBA group in comparison with mice of the oil + DMBA group (P less than 0.01), and neoplastic nodules of the granulosa cell type developed in the unilateral ovary in 10 of 17 mice of the 17 beta-estradiol + DMBA group. No tumors were detected in the mice of the other groups. The plasma levels of both follicle-stimulating and luteinizing hormones as determined by radioimmunoassay were significantly higher (P less than 0.01) in mice of the 17 beta-estradiol + oil group than in mice of the oil + oil group. In Experiment 2, more ovarian tumors of the granulosa cell type were detected before 360 days of age in mice of the 17 beta-estradiol + DMBA group (14 of 18) than in mice of the oil + DMBA group (5 of 15) (P less than 0.05). No tumors developed in mice of the other two groups. These results strongly indicate that an abnormal endocrine milieu caused by neonatal treatment with estrogen may induce a high frequency of transformation of some ovarian tissues and rapid growth of the ovarian tumors after DMBA treatment.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1988

Hormonal characterization of female SL/Ni mice: a small thymus gland strain exhibiting ovarian dysgenesis.

Female SL/Ni mice have a small thymus gland and show accelerated aging of the reproductive system characterized by an early loss of the follicular apparatus and early onset of ovarian tumors. At 9 months of age, circulating levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were higher in the SL/Ni animals than in controls while prolactin (PRL) was lower in the SL/Ni mice. The trends of these hormones are consistent with the loss of the follicular apparatus which is responsible for estradiol production. The high levels of gonadotropins which precede the onset of the tumors confirm the hypothesis that prolonged stimulation by gonadotropins can be a cause of ovarian tumorigenesis. Further, these data suggest that aging of the reproductive system may be a thymus-dependent phenomenon.

Aging↗
PubMed1988

Source of high testosterone levels associated with autoimmune ovarian dysgenesis in neonatally thymectomized B6A mice.

Thymectomy at three days of age (Tx-3) in mice results in early ovarian dysgenesis and eventual sterility. In (C57BL/6JCr x A/JCr)F1 (B6A) mice, the ovaries are reduced in weight, composed mostly of interstitial-like cells, and are usually devoid of oocytes, follicles, and corpora lutea by 60 days of age. This thymectomy-induced acceleration of follicular atresia is autoimmune in nature and is accompanied by circulating auto-oocyte antibodies (AOA). The dysgenesis is also characterized by elevated levels of testosterone (T). To determine the source of these high T levels, various combinations of Tx-3, and adrenalectomy (Adx) and ovariectomy (Ovx) at 15 days of age were performed. Levels of T, estradiol-17 beta (E2), and corticosterone (B) were analyzed and compared with ovarian morphology. Except for plasma B levels, animals that underwent both Tx-3 and Adx were not significantly different from mice that received Tx-3 alone. As anticipated, B and E2 levels were substantially decreased in Adx and Ovx mice, respectively. T levels in the Tx-3 and Tx-3/Adx groups were first elevated at 60 days of age (0.17 and 0.14 ng/ml, respectively) then rose sequentially through 150 days of age (0.91 and 0.89 ng/ml, respectively) as compared to the significantly lower T levels in intact and Tx-3/Ovx mice (less than 0.20 ng/ml through 150 days of age). These results suggest that the increased T is being secreted by ovarian rather than adrenal tissue. Furthermore, this model may be of value to investigators interested in the study of interstitial or non-follicular steroidogenesis in the ovary.

Adrenal Glands↗
PubMed1987

The effect of antisera to thymosin alpha 1 on the course of autoimmune ovarian dysgenesis in neonatally thymectomized mice.

Thymectomy at 3 days of age (Tx-3) in B6A female mice results in an autoimmune oophoritis that has only been successfully overcome by the transplant of an intact thymus or an injection of T cells. In Tx-3 mice levels of thymosin alpha 1 (TSN alpha 1), a potent thymic hormone involved in the development of helper T cells, was previously shown to be high after 7 days. By 60 days levels of TSN alpha 1 returned to levels found in intact mice. By this age ovarian dysgenesis was also complete and accompanied by high circulating levels of auto-oocyte antibody (AOA), estradiol-17 beta (E2) and testosterone (T). In the present study injections of antisera to TSN alpha 1 were given to Tx-3 mice in an attempt to decrease circulating TSN alpha 1 levels. We reasoned that this treatment should inhibit lymphocyte differentiation, and possibly in turn aid in overcoming the ovarian dysgenesis. After treatment of the Tx-3 mice, dysgenic ovaries persisted and high levels of AOA remained similar to the untreated Tx-3 mice. Levels of E2 and T, however, were returned to those found in intact mice. These results suggest that there is a sensitive balance between the thymus and the ovary that may not be related to changes in only a single thymic hormone.

Animals↗
PubMed1987

Cellular events associated with autoimmune oophoritis and ovarian tumorigenesis in neonatally thymectomized mice.

Thymectomy at 3 days of age (Tx-3) in (C3H/HeMs x 129/J)F1 (C31) female mice results in post-pubertal ovarian dysgenesis associated with high levels of circulating auto-oocyte antibodies (AOA) prior to ovarian tumor formation. Evidence suggests that the etiology for the ovarian dysgenesis resulting from Tx-3 is autoimmune and involves helper T cell abnormalities. The present study characterized circulating leukocytes and mitogenic activity using concanavalin A (ConA) with serologically selected spleen T cells. We observed no sustained abnormalities in either number of circulating leukocytes or percentages of granulocytes or lymphocytes. Circulating mononuclear cells with positive immunofluorescence for Thy 1.2 and Lyt 1.1+Lyt 1.2 cell markers were similar in all mice. However, the spleen cells from Tx-3 mice with ovarian dysgenesis remaining after adsorption with antisera to the Lyt 2.1+Lyt 2.2 antigens (helper T cells remaining) showed increased incorporation of [3H]thymidine compared to the intact mice. This stimulated activity occurred during the periods of early ovarian dysgenesis and active tumor growth. Apparently, the autoimmune oophoritis results from an imbalance within the Lyt 1 cells which may represent a primary insult to the ovary that results in later ovarian tumor development.

Animals↗
PubMed1986

Perinatal cannabinoid exposure: effects on hepatic cytochrome P-450 and plasma protein levels in male mice.

Maternal exposure to the major psychoactive delta 9-tetrahydrocannabinol (THC), or to the nonpsychoactive cannabinol (CBN) or cannabidiol (CBD) on day 12 of gestation, or on day 1 postpartum, affected the concentrations of hepatic cytochromes P-450 in adult male offspring. Levels of P-450 were significantly increased in adult males prenatally exposed to cannabinoids, but were reduced after postnatal exposure. The response to exogenous testosterone was also differentially affected by perinatal cannabinoid exposure, with reduced plasma androgen in males prenatally exposed to THC, but increased levels of hormone in mice exposed postnatally to THC or CBN. There was a concomitant decrease in plasma albumin and increased gamma-globulin in adult males postnatally exposed to CBN. Beta-globulin levels were also significantly increased in adult males exposed to cannabichromene (CBC) on day 1 postpartum. Cannabinoid exposure during perinatal periods of development exert effects on hepatic function, plasma androgen levels, and on the immune system. These effects may reflect the ability of perinatal cannabinoid exposure to interfere with androgen-mediated processes of differentiation.

Androgens↗
PubMed1985

Organophosphorus insecticide induced decrease in plasma luteinizing hormone concentration in white-footed mice.

Oral intubation of 50 and 100 mg/kg acephate inhibited brain acetylcholinesterase (AChE) activity by 45% and 56%, and reduced basal luteinizing hormone (LH) concentration by 29% and 25% after 4 h in white-footed mice (Peromyscus leucopus noveboracensis). Dietary exposure to 25, 100, and 400 ppm acephate for 5 days substantially inhibited brain AChE activity, but did not affect plasma LH concentration. These preliminary findings suggest that acute exposure to organophosphorus insecticides may affect LH secretion and possibly reproductive function.

Acetylcholinesterase↗
PubMed1984

Acute endocrine correlates of attack by lactating females in male mice: effects on plasma prolactin, luteinizing hormone and corticosterone levels.

Immediately following defeat inflicted by lactating Rockland-Swiss (R-S) albino mice, adult R-S male mice exhibited significant reductions in circulating prolactin (PRL) and luteinizing hormone (LH), but not corticosterone (CORT). These results suggest that acute neuroendocrine responses to intersex competition may be as dramatic as those previously reported for intermale encounters.

Aggression↗
PubMed1984

Estrogen and thymic hormone interactions in the female mouse.

This study showed that there are relationships between thymic and adrenal/ovarian endocrine actions. A 4 mg/kg dose of thymosin fraction 5 (TSN5) advanced vaginal opening and elevated estrogen levels. Single estradiol benzoate (EB) injections decreased thymus weight and caused a transient reduction in circulating plasma levels of thymosine alpha 1 (TSN alpha 1), a peptide component of TSN5. Circulating estrogen levels were elevated when TSN alpha 1 levels were undetectable. Also, TSN alpha 1 levels decreased with age and after a prolonged athymic state. The thymus was shown to involute after a single TSN5 injection, suggesting the existence of a negative hormonal feedback on the thymus. Additionally thymectomy at 3 days of age was shown to delay vaginal opening while thymectomy at 30 days of age failed to produce any significant effect on reproductive maturation. Although much research is still needed, our results provide additional evidence of a relationship between the endocrine thymus and ovary.

Adrenal Glands↗
PubMed1983

Effects of delta 9-THC and castration on behavior and plasma hormone levels in male mice.

Gonadectomy resulted in a rapid increase in plasma luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels, but had no consistent effects on plasma prolactin (PRL) and growth hormone (GH) levels. In castrated males, oral administration of THC (50 mg/kg) significantly increased plasma LH levels within hours following surgery and again from 3 to several weeks post-castration, while THC treatment decreased LH levels between 1 day and 2 weeks postcastration. Administration of THC to 12-hour sham castrates significantly increased plasma LH levels. Plasma FSH, PRL and GH levels were either reduced or unchanged by THC. Administration of THC significantly reduced levels of gonadotropins, PRL and GH in intact males. In additional studies, we examined the influence of THC on the negative feedback response of the anterior pituitary to gonadal steroids. In testosterone propionate (TP)-treated castrated males, concomitant administration of THC increased plasma testosterone (T) and LH at 20 min, while plasma FSH levels were elevated after 60 min. In contrast, in intact TP-treated mice, concomitant THC exposure reduced plasma T levels except at 60 min, when plasma LH levels were significantly increased. Testosterone replacement failed to restore copulatory behavior in castrated mice given a single dose (50 mg/kg) of THC. In fact, acute THC administration to these TP-treated castrates resulted in marked sedation, which was not observed in intact mice given the same dose of THC in an earlier study. The present findings indicate that the effects of acute THC treatment on pituitary gonadotropin release is dependent upon the time after castration. Furthermore, THC administration can suppress copulatory behavior even in animals whose peripheral T levels have been maintained. Effects of THC on plasma androgen levels in animals injected with TP suggest that THC can alter the metabolism or target tissue response to gonadal steroids.

Animals↗
PubMed1983

Age-related responses to mild restraint in the rat.

Immature, postpubertal, young adult, and middle-aged rats were lightly restrained for 4 h. Relative to untreated controls, restraint uniformly reduced body weight and plasma luteinizing hormone concentration and elevated plasma corticosterone concentration in all age groups. However, restraint increased activities of plasma alanine and aspartate aminotransferase, creatine phosphokinase, and fructose-diphosphate aldolase in only immature and middle-aged animals. This age-related release of tissue enzymes is hypothesized to reflect enhanced responsiveness to catecholamines in immature rats, and possible ischemia related to diminished vasodilatory activity in middle-aged rats. On the basis of these changes, tolerance to restraint in postpubertal and young adults appears to be slightly greater than that of immature and middle-aged rats.

Aging↗
PubMed1982

Ergot drugs suppress plasma levels of prolactin (PRL) but not growth hormone (GH), luteinizing hormone (LH) or corticosterone (CORT) in parturient mice.

Plasma levels of prolactin (PRL), growth hormone (GH), luteinizing hormone (LH), and corticosterone (CORT) were measured in parturient Rockland-Swiss (R-S) albino mice following the daily administration for 10 days of 0.5 mg ergocornine (ERGO), 0.5 mg bromocriptine (BROMO), or sesame oil (OIL). The dams were provided with replete foster young on a daily basis so as to prevent the decline in suckling activity that normally occurs in undernourished pups of ergot-treated dams. Circulating PRL levels were significantly reduced by both ergot drugs but plasma levels of the other hormones measured were not altered. Thus, ergot drugs have relatively specific effects on PRL even in parturient animals receiving sustained high levels of suckling stimulation.

Animals↗
PubMed1981

Changes in hypophyseal hormones associated with accelerated aging and tumorigenesis of the ovaries in neonatally thymectomized mice.

Neonatal thymectomy at 3 days of age in mice results in ovarian dysgenesis, characterized by early follicular and oocyte loss, followed by a high incidence of ovarian tumorigenesis. Thymectomized animals with dysgenetic ovaries had extremely high levels of circulating PRL and gonadotropins before the appearance of the ovarian tumors, supporting the hypothesis that prolonged stimulation by gonadotropic hormones induces ovarian tumors. The levels of LH and FSH, however, were low by the time the tumors actually appeared, indicating a lag period between hormonal stimulation and the actual onset of the tumors. The data suggest that since thymectomized female mice exhibit a hastening of reproductive aging, these animals may be useful models for studying aging of the reproductive system, including the hormonal events which precede tumorigenesis.

Aging↗