Differential effects of testosterone, 5 alpha-dihydrotestosterone and oestradiol-17 beta on plasma concentrations of LH in castrated ferrets

The biological activity of testosterone often depends on the conversion of testosterone within the target cell to an androgenic or oestrogenic metabolite. The purpose of this study was to compare the relative ability of testosterone and two of its metabolites, dihydrotestosterone (DHT) and oestradiol, to suppress LH secretion in castrated male ferrets. Castrated ferrets were treated with five different doses of steroid by implanting various numbers of s.c. silicone elastomer capsules packed with either testosterone, DHT or oestradiol. The lowest dose of oestradiol (0.1 mm capsule length/100 g body weight, mean estimated total release rate of 25 ng/day) significantly suppressed plasma concentrations of LH in castrated ferrets. Higher amounts of DHT (2.5 mm capsule length/100 g body weight, mean estimated total release rate of 88 ng/day) were required for a significant reduction in plasma concentrations of LH. Concentrations of LH were also significantly lowered by testosterone when administered at a 2.5 mm capsule length/100 g body weight; however, estimated total release rate was 312 ng/day from these capsules. The fact that oestradiol was more effective than DHT, and that DHT was more effective than testosterone in inhibiting LH secretion in castrated ferrets, suggests that in gonadally intact ferrets, testosterone may be converted to DHT or oestradiol within target cells that mediate steroid negative feedback on LH secretion.     

Effects of oestradiol-17 beta on testicular microcirculation in rats

The effect of oestradiol-17 beta on testicular microcirculation in intact and hypophysectomized rats was studied before and after treatment with human chorionic gonadotrophin (hCG). Treatment of intact rats with oestradiol-17 beta for 5 days did not influence vasomotion but decreased testicular interstitial fluid volume (IFV). Treatment of intact rats with 50 IU hCG 8 h before the experiment began induced an increase in testicular IFV, abolished vasomotion and increased the accumulation of polymorphonuclear leucocytes in the testicular venules and interstitium. These changes were unaffected by pretreatment with oestradiol-17 beta, despite the decreased testosterone production. However, pretreatment with oestradiol-17 beta potentiated the hCG-induced migration of polymorphonuclear leucocytes to the interstitium. The interstitial fluid volume and number of polymorphonuclear leucocytes in blood vessels were decreased in hypophysectomized rats, and vasomotion was abolished. Daily treatment with 5 IU hCG increased the IFV and the number of polymorphonuclear leucocytes in blood vessels, and preserved vasomotion. Treatment of hypophysectomized rats with oestradiol-17 beta decreased testosterone production but did not influence basal IFV, vasomotion or the changes in IFV and vasomotion induced by 5 IU hCG. The present study shows that the regulation of testicular vascular permeability and vasomotion may not be directly related to testicular steroidogenesis, and that oestrogens are probably not involved as a mediator of the hCG-induced changes in testicular microcirculation.     

Comparison of morphological and biochemical indicators of prostatic growth and function in castrated rats receiving separately and simultaneously 5 alpha-dihydrotestosterone and 5 alpha-androstane-3 beta, 17 beta-diol

Experiments in vito showed that indicators of prostatic growth (organ mass, protein content, DNA) and function (acid phosphatase activity) of castrated rats regenerated under the influence of 5 alpha-dihydrotestosterone. The morphological structure of this organ showed a pronounced activation of the glandular epithelium proliferation by this metabolite without a significant effect on the connective tissue. The other testosterone metabolite 5 alpha-androstan-3 beta, 17 beta-diol did not influence biochemical indicators but according to the morphological data it stimulated the secretory activity of the glandular epithelium and connective tissue formation. As a result of a combined effect of the metabolites the influence of 5 alpha-dihydrotestosterone on the proliferative processes in the prostate was limited, and the response of the connective tissue to 5 alpha-androstan-3 beta, 17 beta-diol preserved. The results obtained were not in accord with a hypothesis that 5 alpha-dihydrotestosterone is the only physiologically active testosterone metabolite in the rat pancreas, and confirmed the idea of androgen functional interrelationship.     

Responses of the anterior pituitary of ovariectomized rats to oestradiol-17 beta administration

The response of the female rat anterior pituitary gland to oestradiol-17 beta administered sc by silastic capsule implants (6-120 microgram/day) has been examined. Cholesterol, oestradiol-17 alpha, and testosterone were used as control hormone implants. The biochemical changes in the gland as assayed by DNA, RNA, and protein contents were monitored at intervals of 7, 21, 42, and 120 days. In addition, the number of cells per gland was determined by an experimental cell counting technique and correlated to the number of cells based on total DNA content. These results extend previous observations of the hypertrophy of the anterior pituitary and show essentially parallel increases in cell number, DNA, RNA, and protein contents.     

Metabolism of oestradiol-17 beta and oestrone in the human uterus.

A study of the metabolism of oestradiol in the human endometrium and myometrium of the proliferative and secretory phases of the cycle showed that the conversion of oestradiol to oestrone by endometrium in the proliferative phase was higher than that in the secretory phase. The decreased metabolic activity of the secretory phase endometrium was attributed to the influence of progesterone on the endometrium. The metabolic conversion of oestradiol to oestrone was enhanced when pyridine nucleotides were added to the system. The conversion of oestradiol to oestrone was maximum in the cytoplasmic and nuclear fractions of the endometrium. Furthermore, the conversion of oestradiol was low in all the subcellular fractions of the myometrium as compared with the endometrial subcellular fractions. The presence of co-factors increased the metabolic conversion of oestradiol to oestrone in the subcellular fractions of the endometrium. The presence of 17 beta-hydroxysteroid oxidoreductase was indicated in all the subcellular fractions. A correlation was found between the amount of oestradiol and oestrone bound to the receptors in the uterus and the rate of metabolism of oestradiol in the uterus. The physiological significance of metabolism of oestradiol and the hormone action are discussed.     

Effects of oxytocin and vasopressin on the ovarian blood flow, progesterone and oestradiol-17 beta secretion in oestrous rats

Oestrous rats were anaesthetized with pentobarbital, one of the femoral arteries and veins and one of the ovarian veins were cannulated, and a thin polyethylene cannula was fixed in the ovarian bursa. Five-min blood fractions were collected from the ovary for 50 min. Following the control fractions 15 mU of oxytocin, 15 mU of vasopressin or 50 microliter of 0.9% NaCl solution was given into the ovarian bursa over 10 min. Blood pressure and ovarian blood flow were continuously recorded. Progesterone (P) and oestradiol-17 beta (E2) were determined from the blood samples by RIA. Oxytocin did not alter the blood pressure, whereas the ovarian blood flow showed a short increasing tendency. Later, however, it started to decrease in parallel with the decrease in blood pressure owing to blood loss. The secretion of P and E2 remained unchanged. No changes in blood pressure were observed after vasopressin administration, although the ovarian blood flow quickly decreased in parallel with the secretion of P and E2. It is suggested that oxytocin has no direct effect on ovarian blood flow and hormone secretion in the rat. Vasopressin, however, is an effective vasoconstrictor in the rat ovary and may in this way reduce hormone synthesis.     

Oestrone, oestradiol-17beta and oestriol levels in human foetal plasma during gestation and at term

Marked rises in both unconjugated and sulphoconjugated estrone, estradiol-17-beta and estriol were observed in human fetal plasma between midgestation and term. Significant arterio-venous differences were found in the umbilical cord plasma. No consistent arterio-venous differences were found in the umbilical cord plasma. This indicates that all 3 estrogens are secreted from the placenta into the fetal circulation in the unconjugated form. Mean unconjugated estrogen (estrone + estradiol-17-beta + estriol) levels rose from 22.7 ng/ml at 17-20 weeks of gestation to 108.9 ng/ml at term in umbilical venous plasma and from 4.3 ng/ml to 23.3 ng/ml in umbilical arterial plasma. This represents a secretion rate of approximately 30 mg estrogen/day into the umbilical vein at term. Mean estrogen sulphate levels rose from 128 ng/ml to 313 ng/ml in the cord plasma during the same period. Of the 3 estrogens measured, estriol was quantitatively the major estrogen in fetal plasma. It consistently represented about 78% of the unconjugated fraction and 95% of the sulphate fraction at all stages of gestation. The method of delivery did not have a significant effect on the estrogen levels in uncomplicated pregnancies. Similar estrogen levels were found in fetal heart blood after either hysterotomy at spontaneous abortion at 16-20 weeks of gestation, and no significant differences were found for estrogen levels in cord plasma after elective Caesarean section at 38-39 weeks when compared with estrogen levels after normal delivery at term. A significant rise in fetal unconjugated estrogens at a time when fetal corticosteroids are increasing may be of physiological importance for fetal maturation in women.