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T G Muldoon

Publications and source records attributed to T G Muldoon.

71 records · Page 4Linked to original sources
PubMed1976

Actions of pregnant mare serum gonadotropin in the immature female rat: correlative changes in blood steroids, gonadotropins, and cytoplasmic estradiol receptors of the anterior pituitary and hypothalamus.

Several blood steroids, serum gonadotropins and cytosol estradiol receptors of the anterior pituitary and hypothalamus were quantified in immature female rats which were induced to ovulate with pregnant mare's serum gonadotropin (PMSG). Studies revealed that serum levels of progesterone, 17-hydroxyprogesterone, testosterone, androstenedione and estradiol were initially elevated at 6 PM (day 30) after administration of 8 IU of PMSG at 10 AM day 30. Serum levels of estradiol and testosterone rose progressively from day 30 through the AM of day 32. A further increase in serum concentrations of progesterone, 17-hydroxyprogesterone, androstenedione, testosterone, and dehydroepiandrosterone occurred on the PM of day 32 whereas serum estradiol levels declined. Serum levels of all steroids declined on the day of estrus (33) and only progesterone levels were further elevated on day 34 (diestrus). Dihydrotestosterone concentrations were minimally altered by PMSG treatment. Saline administration resulted in no significant alterations in levels of any steroid quantified from day 29 to 34 in control animals. A progressive decline in cytosol estradiol receptor content of the anterior pituitary and hypothalamus was documented following PMSG treatment of intact female rats; there was no depletion of receptors following PMSG administration to ovariectomized immature rats. Maximal depletion of cytosol estradiol receptors occurred on day 32 with replenishment of cytosol estradiol receptor levels on estrus (day 33). The preovulatory gonadotropin surge was found to occur on the PM of day 32 after maximal receptor depletion. The cycle of depletion and replenishment of receptors was repeated during a second spontaneous estrous cycle four days later which coincided with a rise and fall in serum estradiol levels. It is suggested that the depletion of cytosol estradiol receptors of the anterior pituitary/hypothalamic unit may be causally related to the preovulatory gonadotropin surge resulting from PMSG administration to immature female rats. In addition, changes in blood steroids and gonadotropins after PMSG treatment are similar to those reported for proestrus-estrus-diestrus I of the normal adult estrous cycle. These findings further demonstrate the validity of the PMSG-primed immature female rat preparation as a model for the estrous cycle of the adult rat.

Androstenedione↗
PubMed1976

Sex-related differences in the regulation of cytoplasmic estrogen receptor levels in responsive tissues of the rat.

Cytoplasmic estrogen receptors were measured in the anterior pituitary and hypothalamus of intact adult Holtzman male and female rats at various time intervals following injection of 10 mug of 17beta-estradiol. Following equivalent depletion of receptors at 1 h in either sex, replenishment of cytosol receptor levels progressed at a greater rate and to a higher level in the male than in the female. Cycloheximide only partially inhibited replenishment, and its blocking effect was similar in males and females. The administration of 5 mug of 17beta-estradiol to adult males elicited less depletion than did 10 mug, and a completely cycloheximide-sensitive replenishment phase. Patterns of depletion and replenishment in immature rats following 0.1 mug of 17beta-estradiol were the same for males and females. In an analysis of the effects of neonatal androgenization, Charles River rats were used and it was initially demonstrated that no sex differences in receptor levels existed between normal males and females. After an injection of an androgenizing level of testosterone propionate on day 3 of age, a full normal complement of receptors was found in estrogen-responsive tissues at 90--100 days of age. The functional dynamics of receptor depletion and replenishment under the influence of exogenous estrogen, however, indicated that the anterior pituitary of the androgenized female responded differently from that of the untreated female, and similarly to that of the male. The hypothalamic receptor dynamics in the male were unaltered by early androgen administration, but estrogen-induced depletion of receptors in the female hypothalamus was considerably less extensive in the androgenized animal than in the untreated control. Whereas cytoplasmic estrogen receptor levels are essentially independent of sex in the rat, the present results indicate a sex-linked difference in the dynamics of receptor turnover in the anterior pituitary and hypothalamic response to 17beta-estradiol.

Animals↗
PubMed1975

Inhibition of anterior pituitary estrogen-receptor complex formation by low-affinity interaction with 5 alpha-dihydrotestosterone.

A possible role for 5alpha-dihydrotestosterone in the anterior pituitary of the rat has been investigated by determining the influence of this androgen upon the binding 17beta-estrasiol to its cytoplasmic receptor. Under equilibrium binding conditions, both testosterone and 5 alpha-dihydrotestosterone are very poor competitors for the estrogen binding sites, as compared to estrogenic compounds. 5alpha-Dihydrotestosterone, however, inhibits the initial rate of formation of the estradiol-receptor complex in a concentration-dependent manner. Steroidal specificity of this incubation is indicated by the failure of progesterone to elicit the same effect. The androgen inhibition appears to involve low-affinity interaction with the estrogen receptor, since no high-affinity binding of 5alpha-dihydrotestosterone could be detected. Kinetic analysis indicated that the inhibition is competitive, involving interaction at the estrogen-binding site of the receptor.

Animals↗
PubMed1975

Modulation by thyroid hormones of cytoplasmic estrogen receptor concentrations in reproductive tissues of the rat.

The influence of induced variations in circulating levels of thyroid hormones upon the estrogen receptor content of rat uterine, anterior pituitary and hypothalamic cytosol fractions has been investigated. Sucrose gradient centrifugation analyses showed no observable effects of thyroidectomy or acute induced hyperthyroidism upon receptor levels in uterus hypothalamus of ovariectomized rats, but an apparent positive thyroidal influence upon anterior pituitary receptor content. Qualitatively, the receptor complex sedimentation coefficients were unaltered. Binding assays showed that thyroid hormone administration to the ovariectomized rat resulted in a marked increase in pituitary receptor content, whereas the same treatment had no significant effect on the pituitary receptor level of the intact animal. Conversely, a marked fall in uterine receptor content was found in thyroxine-treated intact, but not castrate, animals. The changes in measurable receptor levels could not be attributed to competition for estrogen binding sites by thyroxine or triiodothyronine. Pituitary receptor content of ovariectomized rats was studied following administration of varying levels of thyroxine; 5 mug/day significantly depressed receptor levels, while enhancement of binding capacity was occasioned by levels of thyroxine ewual to or greather than 25 mug/day. The hypothalamus was completely unaffected by similar treatment and the uterus responded with decreased receptor level only at the highest dosage used. Thyroxine replacement reversed the decrease in anterior pituitary receptor concentration detectable following thyroidectomy. The effect of the thyroid hormones on the pituitary receptor content was not a result of changes in the capability of the tissue to respond to estrogen-induced synthesis of receptor.

Animals↗
PubMed1975

Development of thyroidal responsiveness to estrogen in the maturing rat (38471).

The incidence of thyroid disorders around the time of puberty is frequent in human females. The influence of estrogen on thyroid function during this period has been controversial. Female rats hypophysectomized at 21, 30 or 50 days of age were treated with either 17beta-estradiol (E-2) or TSH or a mixture of E-2 and TSH. Determinations were then made of thyrodial 131I-uptake, organic 131I, and 131I excretory patterns. In 21-day old animals, E-2 alone had no effect on thyroidal 131 I uptake, whereas in 30-day or older animals E-2 significantly increased 131I uptake. TSH or TSH-E-2 combinations markedly increased 131I uptake in both groups. Thyroidal 131I was shown to be almost exclusively protein-bound in each instance. No difference was observed between 21 and 30-day old rats with respect to 131I excretory patterns,except for decreased urinary output in the TSH-E-2 groups; this decrease, however, appeared to be partially attributable to an increased thyroidal uptake of iodine in these animals. The results suggest that the thyroid gland becomes responsive to estrogen only at or around the time of puberty.

Age Factors↗
PubMedDate not supplied

Structure-activity relationships of some unique estrogens related to estradiol are predicted by fit into DNA.

The estrogenic activity of 11 beta-acetoxy estradiol, 11 beta-hydroxy estradiol, 11 alpha-hydroxy estradiol and 9 beta-estradiol was compared to estradiol using the restoration of uterine weight and prevention of LH rise in immature ovariectomized rats as endpoints of the assay. There was a good correlation between results using the two methods and estrogenic activity was found to be in the following order: 11 beta-acetoxy estradiol greater than estradiol greater than 9 beta-estradiol greater than 11 beta-hydroxy estradiol greater than 11 alpha-hydroxy estradiol. The biological activities of these compounds could be explained on the basis of stereochemical complementarity to the structure of DNA.

Animals↗