Henry M. Lemon

Studies in steroid metabolism: XVIII. Evidence for the conversion in vitro of [4-14C]testosterone to 17β-hydroxy-[4-14C]5α-androst-1-en-3-one by human prostate

Abstract A comparison of [4-14C]testosterone transformation products derived from incubations with human prostatic and fetal-liver minces has been made and observed differences in the metabolite patterns are described. Our evidence for the conversion in vitro of [4-14C]testosterone to 17β- hydroxy -[4- 14 C]5α- androst -1- en -3- one on incubation with surgically removed, benign hypertrophic human prostate consists of the following findings: 1. 1. Carrier steroid, prepared by 2 synthetic routes, and the biological metabolite had the same mobilities in the paper-chromatography system ligroin-propylene glycol and gave on paper the same characteristic colors with the alkaline m- dinitrobenzene reagent. 2. 2. The thiosemicarbazone derivatives of both carrier and metabolite in ethanolic solution had absorption maxima at 298 mμ. 3. 3. Column partition chromatography established identical retention volumes for synthetic 17β-hydroxy-5α-androst-1-en-3-one and for the [4-14C]testosterone transformation product; chromatography of a mixture of carrier and radiometabolite yielded superimposable elution curves. The extract of the prostatic incubate also contained a radioactive component with the paper-chromatographic mobility of 5α-androst-1-ene-3,17-dione. No evidence for the presence of Δ 1 -3- ketones could be found in human-fetal-liver digests of [4-14C]testosterone.

Endocrine function in bronchial asthma and hay fever: A controlled study of 17-ketosteroid and 11-oxysteroid excretion

Abstract A controlled study of 17-ketosteroid and 11-oxysteroid excretion in ambulatory patients with bronchial asthma has been carried out during intervals when the patients had been without steroid medication for at least two weeks. No significant correlation was noted between steroid excretion and the asthmatic state as verified by serial timed vital capacities and daily score sheets. No significant correlation was noted between 17-ketosteroid excretion and 11-oxysteroid excretion. Total 11-oxysteroid excretion was not abnormal in bronchial asthma. Significant reduction of total 17-ketosteroids was found in both male and female asthmatic patients, as compared to age- and sex-matched controls, but not in patients with hay fever. Fractional 17-ketosteroid excretion as measured by androsterone-glucuronide and etiocholanolone-glucuronide analyses tended to confirm total 17-ketosteroid excretion. The administration of cortisone resulted in a further decrease of androsterone-glucuronide and etiocholanolone-glucuronide excretion for the duration of therapy.

Studies in steroid metabolism. IV. Evidence for the formation of a water-soluble conjugate during in vitro incubations of human tissue with testosterone.

Abstract 1. 1.Evidence has been presented for the formation of a water-soluble conjugate during the 2. in vitro incubation of human prostatic tissue slices with testosterone and 4 - 14 C-testosterone. 3. 2. It was shown that the steroid conjugate was hydrolyzed by a commercial preparation of β-glucuronidase (Warner-Ketodase) of unknown purity. 4. 3. By carrier dilution technique it was established that the steroid moiety of the conjugate was testosterone.

ABDOMINOVAGINAL ELECTROPOTENTIAL DIFFERENCES IN THE MENSTRUAL CYCLE

A revised technique using a simplified electrode and a recording millipotentiometer that does not draw current from its external circuit for pinpointing electropotential changes of the ovary to determine ovulation is presented along with some clinical applications and observations. The recording instrument was a vacuum tube recording millipotentiometer of high resistance that measures changes in potential differences between a glass electrode inserted in the vagina and a similar reference electrode in the anterior abdominal wall. Instrument is grounded to patients leg. Potential changes are transferred from the liquid electrode through calomel half cells to reach the recording instrument. The following generalizations have been made based on vaginal recordings of nearly 3000 tests. 1) A marked difference in recordings of electrovaginal potential was found between normal premenopausal and postmenopausal women. 2) After menstruation normal women showed successive daily changes in initial electropotential differences and the type of curve recorded 3) Voltages for premenopausal women are maintained in the negative range. 4) Readings were reproducible from patient to patient and from day of 1 cycle to corresponding day of the next. 5) No cyclic variations were found in postmenopausal women and voltages may appear in the negative or positive range. The following characteristics of curves in different stages of the menstrual cycle were noted: 1) postmenstruation--no potential difference (flat curve) with voltages in negative range from minus 20-minus 8 mV; variations in baseline levels noted; 2) preovulatory--curve rises sharply just before ovulation from minus 20-plus 20 or 30 mV; 3) ovulation--curve remains flat and recordings remain in positive range (12-22 mV) for 1-2 days (this is thought to be ovulation); 4) postovulatory--same curve as preovulatory with curve rising sharply from negative to positive readings; 5) premenstrual--relatively flat curve with readings in the range of minus 4-minus 10. Possible clinical applications of this method include breast cancer detection ovarian cyst detection determination of ovulation and fertility control.

Control of pain in metastatic cancer

Abstract A multiphasic approach to cancer pain control is outlined, utilizing prophylactic palliative surgery or x-ray therapy when necessary. Hormone therapy acts synergistically with local irradiation or systemic radiomimetic agents for pain relief from breast, prostate, thyroid, and ovarian neoplasms. Synthetic morphine derivatives often adequately control pain without development of excessive requirements until near the patients death. Morphine or other opiates remain the best agents for terminal care in cases which have not become tolerant by premature resort to these drugs.