Gray H. Twombly

The biosynthesis of labeled estriol-3-sulfate-16-glucosiduronate ☆

Abstract Estriol-3-sulfate-16-glucosiduronate (E 3 SG) was prepared by incubating estriol-16-glucosiduronate in a 100,000 × g supernate of homogenized guinea pig liver in the presence of ATP and MgSO 4 . The E 3 SG was purified by countercurrent distribution. A high degree of purity was demonstrated by gradient elution chromatography on celite, high voltage paper electrophoresis, paper chromatography in 2 solvent systems and enzyme hydrolysis.

Metabolism of estrone-C14-16 sulfate in women☆

Abstract 1.1. Radioactive sodium estrone sulfate has been synthesized with C 14 at Position 16 in the steroid nucleus. Material has been used giving up to 18.4 million counts per minute per milligram in a windowless glow gas counter. 2.2. Comparative studies of urinary excretion of radioactive metabolites in patients taking this material by mouth with others taking radioactive estrone in oil show a much higher absorption of sodium estrone sulfate than of estrone. Fifty-five per cent of the ingested radioactivity appears in the urine at 48 hours, compared to 16 per cent or less for estrone. 3.3. Sodium estrone sulfate and estrone produce the same kind of metabolites in the urine in roughly the same quantities, suggesting that they are interconvertible within the body. 4.4. Sodium estrone sulfate given by mouth appears soon thereafter in the bile and in the urine. The quantities excreted by each route are roughly the same. At first the excretory products contain considerable sulfate. Later, they are largely glucuronides. 5.5. Sodium estrone sulfate injected into the body disappears very rapidly and probably becomes localized somewhere in the tissue.

Endometrial cancer, obesity, and estrogenic excretion in women

Abstract Fifty-two women were injected with estradiol-17β-16-C 14 and the radioactivity of their urine determined at 72 hours. They excreted 28 to 92 per cent. Twenty-two women weighing 150 pounds or less excreted an average of 68 per cent of the injected radioactive carbon in 72 hours. Thirty obese women, 150 to 240 pounds in weight, excreted an average of 56 per cent in 72 hours. There seemed to be a statistically significant correlation between weight and percentage excretion; the thinner the patient, the higher the rate of excretion. In 2 patients, 15 and 18 hours after intramuscular injection, considerable quantities of radioactivity were found in the fat. The theory is propounded that cancer of the endometrium, if it is due to chronic estrogenic stimulation, may occur in obese women frequently because these individuals store estrogens in their fat and possibly thereby prolong the effect of their own hormones on their own endometria.

The innervation of the bladder with reference to radical hysterectomy

Abstract 1.1. Complete parasympathetic denervation of the bladder is unusual during radical hysterectomy. It may occur if the surgeon strips the sacral nerves bilaterally, or excises a major portion of the paracervical and paravaginal web of retroperitoneal tissue. 2.2. The parasympathetically denervated bladder is not flaccid, but has tone and capacity. It has no thermal sensation. Initially it has no voiding contraction. After a latent period of weeks or months, if not damaged by prolonged overdistention, it may develop rhythmic contractions and periodic sluggish voiding contractions. These latter may be perceived by peritoneal or urethral sensation, voluntarily opposed by contraction of urethral striated muscle and augmented by contraction of abdominal muscle. 3.3. It is not unlikely that eventually normal function may be re-established in some patients by the regeneration of some of the interrupted fibers.

Estrogen storage in fat

Abstract When 14 C-labeled estradiol is injected intravenously into obese women, unconjugated labeled estrogens will be found in their body fat, the amount roughly proportional to the weight of the fat. The half-life of these stored hormones is about 10 hours. Rabbits implanted with pellets of estradiol occasionally develop carcinoma of the endometrium (4 of 20 in 219 to 597 days), but this continuous type of stimulation seems no more effective than intermittent injections as used by Meissner, Sommers, and Sherman. 11 CBA mice made obese by injection of gold thioglucose go into constant estrus and show hypertrophied uteri. They do not stay in estrus any longer, however, than do normal controls following castration. Obese Vob mice show no evidence of chronic estrogenic stimulation. Pregnant women at term have no evidence of stored estrone, estradiol, or estriol in their body fat. The level of these hormones appear to be somewhat less gram for gram than those found in their serum. Our observations suggest that obesity is a concomitant phenomenon and not a cause of cancer of the endometrium.

Interconversions of 16-oxygenated estrogens. II. The metabolism of 16-ketoestradiol-17β-16-C14 in man

Abstract 16-Ketoestradiol-17β-16-C 14 was administered to two human subjects. About 65% of the radioactivity was excreted in the urine within 24 hr. largely in the form of glucuronide conjugates. Virtually the entire radioactive glucuronide fraction consisted of 16-ketoestradiol-17β, estriol, and 16-epiestriol, the respective ratios being 1:2.6:0.6.

Spontaneous regression of advanced endometrial carcinoma

The phenomenon of spontaneous regression of cancer is rarely seen or proven, but the sporadic cases reported encourage scientists from the various fields of human biology to search for an explanation for these amazing anecdotal events. Metastatic endometrial carcinoma has a grave prognosis and few patients survive more than 5 years. A case of Stage IV endometrial carcinoma in a patient who received partial treatment but has survived for 18 years without evidence of disease is presented. Apparently, spontaneous regression does occur, although the characteristics of such a phenomenon are yet unknown.