Total Gonadotrophic Activity Research Articles

Pituitary-gonadal interrelationships in pubertal female subjects.

ABSTRACT Hormone assays in urine were conducted serially in four girls for 28 to 78 days each year for a period of four or five years. Assays of the three classical oestrogens and pregnanediol were made throughout this time; total gonadotrophins were estimated during the first two years and FSH and/or LH in subsequent years. Oestrogen output rose gradually throughout, evidence of variation in hormonal activity being noted from the second year onwards. In two of the girls who menstruated in the fourth year, the pattern of oestrogen excretion was similar to that of adult women during reproductive life. Pregnanediol output was generally low, tended to rise with increasing age, and from the second year onwards levels fluctuated. Ovulation, as judged by pregnanediol assays, occurred in two out of the nine cycles studied. Total gonadotrophic activity was low in the first year and rose in the second. In the third year FSH output was at the lower end of the range of values occurring in young normally menstruating women and was within this range during the fifth year. LH activity was low when first estimated, rose slightly in the fourth year, and showed a typical adult pattern, including a midcycle peak, in the fifth. The investigation demonstrated a progressive rise in steroid and gonadotrophin output in pubertal female subjects as they increased in stature, developed secondary sex characteristics and approached the menarche; the increase was associated with marked fluctuations in hormonal activity well in advance of the first menstrual bleeding. The physiological significance of these bleedings is discussed, and it is emphasised that the study as a whole provides a useful framework for the investigation of pathological conditions occurring at or about the time of puberty.

Gonadotrophic activities of anterior pituitary and of blood plasma and ovarian response to exogenous gonadotrophin in moulting hens.

Summary. The total gonadotrophic activities of the anterior pituitary glands and blood plasma of hens, Gallus domesticus, during the moulting period were estimated using the assay method based on the weight increase of chick testis. The activities in both the pituitary and the blood of hens in the four groups classified according to the progress of moult were significantly higher than those of laying hens. Nevertheless, no detectable level of serum vitellin and a completely regressed ovary were found in moulting hens. Anterior pituitary glands of moulting and laying hens were assayed for their fsh and lh activities by the use of the hcg augmentation method or the ovarian ascorbic acid depletion test. The fsh activity of the moulting hen was about twofold higher than that of the laying hen, whereas lh activity was about equal during the moulting and the laying periods. The serum vitellin of moulting hens increased steeply with the injection of oestrogen over 3 days. When chicken anterior pituitary homogenate was injected once daily for 6 days to hens in the moulting period, a satisfactory follicular growth as in the laying hen was induced in all of the treated hens. Injection of pmsg into moulting hens for 6 days resulted in an increase of serum vitellin in all the hens and the formation of yellow follicles in 40% of the treated hens. These results suggested that the failure of follicular growth in the moulting hen, despite high levels of total gonadotrophic activity in both pituitary and blood, might be due to an unbalanced secretion of endogenous gonadotrophins.

The occurrence of the syndrome of anorexia nervosa in male subjects.

SynopsisA syndrome characterized by the psychopathological features of anorexia nervosa occurs in male subjects. There have been 25 cases previously reported in the literature which appear to be fairly typical of the condition and the present paper adds the case histories of another six patients. Endocrine investigation on these patients reveals a disorder of urinary excretion levels of testosterone and of total gonadotrophic activity, which is comparable to the disturbance of sex hormones that accompanies the menstrual disturbance of female patients with anorexia nervosa. The exact nature of the endocrine disturbance in the male, however, is still less well understood than that in the female.

ENDOCRINE PROFILES IN PREMENSTRUAL TENSION

SUMMARYStudies on pituitary and ovarian function as assessed by the urinary output of total gonadotrophic activity, the three classical oestrogens, pregnanediol and, in some cases, testosterone and epitestosterone, were conducted in eight patients suffering from premenstrual tension. Major abnormalities in endocrine function were not a feature of the condition. Ovulation, as judged by pregnanediol assays, was absent in seven out of the fifteen cycles investigated. Contrary to traditional belief, the symptoms of premenstrual tension could exist in the presence of cycles with anovulatory hormonal patterns.

Psychological and nutritional factors in disturbances of menstrual function and ovulation.

Evidence has shown that amenorrhea can be induced by emotional upheavals such as are present during wartime psychiatric illness such as schizophrenia and feeding disorders. Anxiety in potential gas chamber victims induced amenorrhea in 54% of women. Food deprivation in Holland between 1944 and 1945 caused menstruation cessation in 50% of urban women. In feeding disorders such as anorexia nervosa a 100% occurrence of amenorrhea has been reported. Hormonal studies in anorexic patients show abnormal total gonadotrophic activity (TGA) low basal levels and absent cyclical fluctuations. Results of a study of obese patients treated with a weight-reducing regimen suggest that food restriction and weight loss are more influential in lowering the basal levels of TGA and less significantly influential on cyclical activity. Studies done on some species of animals suggest that basal levels and TGA cycles are controlled by different central nervous mechanisms. To what extent these mechanisms affect amenorrhea of emotional origin and anorexia nervosa are still unknown but an association has been made between amenorrhea and emotional or psychiatric illness and feeding disorders.

ENDOCRINOLOGICAL STUDIES IN FOUR NORMAL GIRLS THROUGHOUT THE PREPUBERTAL PERIOD OF LIFE

Hormone assays in urine were conducted in four girls each of whom was aged 10 at the commencement of the investigation. Serial determinations were performed for periods ranging from 28 to 78 days at the same time each year for four or five years. Throughout the whole investigation assays of the three classical oestrogens and of pregnanediol were made. During the first two years assays of »total gonadotrophic activity« were conducted, while in subsequent years FSH and/or LH were measured.

Gonadotrophin excretion in ovariectomized bitches.

Summary. Results of urinary assays of total gonadotrophic activity, fsh and lh in ovariectomized Beagle bitches are reported. Urine samples collected from animals in metabolism crates were extracted by the tannic acid precipitation technique. Very low levels of total gonadotrophic activity were found when the mouse uterus test was employed; activity being undetectable in six out of thirteen animals. Levels of fsh could generally be measured by the mouse ovarian augmentation test. In a group of six bitches, the individual means for fsh output ranged from <4·5 to 21·6 i.u./24 hr. Levels of lh were assayed by the ovarian ascorbic acid depletion test in a series of ten animals and values ranged from <5·0 to 10·4 i.u./24 hr.

Gonadotrophin excretion at puberty.

Studies relating the pattern of gonadotrophin excretion to the development of sexual maturity in the human female are few in number and contradictory. Some investigators have been unable to detect by bioassay any gonadotrophic activity in the urine of boys and girls (Albert, 1956; Wilkins, 1965). Others (Brown, 1958; Kulin, Rifkind, Ross & O'Dell, 1967) have found measurable gonadotrophic activity in the urine of prepubertal children; this was present for at least 1 yr (Catchpole & Greulich, 1943) and even up to 2½ yr (Johnsen, 1959) before the menarche. These gonadotrophin levels were usually lower than the average concentrations in the adult. Little or no information is available as to the time of onset of rhythmical secretion of pituitary gonadotrophins in man. It is the purpose of this communication to describe the cyclical pattern of excretion of total gonadotrophic activity in a 12-yr-old girl during the 3 months before the

STUDIES ON PITUITARY GONADOTROPHINS IN HUMAN PLASMA

ABSTRACT Plasma pools obtained from men and postmenopausal women were extracted by an ammonium acetate-ethanol procedure and assayed by four biological systems assumed to measure »total« gonadotrophic activity, follicle-stimulating or luteinizing hormone activity. The 2nd International Reference Preparation for Human Menopausal Gonadotrophin, NIH-FSH-S2 and NIH-LH-S3 were used as standards. All assays were valid with regard to the statistical tests performed. Postmenopausal plasma contained 17 times more total gonadotrophic activity, 15 times more FSH activity and 4–6 times more LH activity than male plasma. The FSH/LH ratio was 2–4 times higher in postmenopausal than in male plasma. When postmenopausal plasma was calculated in terms of male plasma, the biological dissimilarity of the two materials was also indicated by the indices of discrimination for combinations of assays, which were significantly different from unity for all groups measuring a relationship FSH/LH.

The relationship of gonadotrophin excretion to ovulation during the menstrual cycle.

ABSTRACT Serial determinations of urinary gonadotrophins, oestrogens and pregnanediol have been performed in one cycle from each of seven normally menstruating women. In all cycles there was evidence of ovulation as judged by steroid excretion although the actual time at which this event occurred varied considerably between individuals. Assays of »total gonadotrophic activity« by the mouse uterus test were conducted in two subjects. In only one woman was a midcycle peak noted. Follicle-stimulating hormone (FSH) was measured in five cycles. In four, levels tended to be higher at midcycle than at any other time although a definite peak of excretion was noted in only two of these. In the fifth subject FSH excretion was relatively constant throughout the period of investigation. Luteinising hormone (LH) was estimated in four cycles. In two a definite peak of excretion occurred but in only one was this closely associated with ovulation. In the remaining two women the midcycle LH peak was less pronounced. No definite correlation could be demonstrated between the excretion of FSH, LH and »total gonadotrophic activity« on the one hand and urinary steroid output on the other.

THE URINARY EXCRETION OF GONADOTROPHINS BY SHEEP: THE EFFECT OF SOME NUTRITIONAL FACTORS ON THE EXCRETION OF GONADOTROPHINS BY CASTRATED MALE SHEEP.

SUMMARY Male castrated Merino sheep were fed indoors on a dry ration or grazed on a good quality pasture. Despite the much greater urine volumes excreted by the grazing animals, the mean daily rates of excretion of total gonadotrophic activity and follicle-stimulating hormone (FSH) were very similar in the two groups. Corresponding levels of excretion of luteinizing hormone (LH) were very variable, owing apparently to deficiencies in the assay technique. When sheep were fed indoors on freshly cut grass, the urine output was almost three-quarters of that of grazing animals but the rate of excretion of total gonadotrophic activity and of FSH was considerably greater than that of grazing animals. The daily output of urine by sheep fed indoors on a dry ration was adjusted to equal that of grazing sheep. Although the amounts of total gonadotrophic activity were smaller than those in the previous experiments, the amounts of FSH excreted were the highest recorded in the entire investigation. The possibility of a temporal fluctuation in the excretion of gonadotrophins is discussed.

THE URINARY EXCRETION OF GONADOTROPHINS BY SHEEP: EXTRACTION PROCEDURE AND DAY-TO-DAY FLUCTUATION IN EXCRETION BY MALE AND FEMALE CASTRATED SHEEP.

SUMMARY The application of Johnsen's tannic acid method to the extraction of gonadotrophins from ovine urine was studied using the urine of castrated sheep. Slight modification of the original method increased the efficiency of extraction. Rate of recovery was measured at several levels of added pituitary and urinary gonadotrophins and was similar to recovery rates reported for human urines (30–81 %). Reproducibility of the extraction procedure was excellent. Further purification of the final ethanol precipitate without loss in potency was effected by chromatography using diethylaminoethyl cellulose. The daily excretion of total gonadotrophic activity, follicle stimulating hormone and luteinizing hormone by two male and one female castrated sheep was estimated for four periods each of 3 weeks. In all instances excretory levels fluctuated considerably and randomly. Levels of excretion of all types of gonadotrophic activity were much lower than in man.

Gonadotrophins of pituitary origin in the urine of sheep after castration and ovariectomy.

ABSTRACT Gonadotrophic activity has been detected in the urine of castrate male and ovariectomized female sheep. The kaolin-acetone methods of Loraine &amp; Brown (1956) and of Albert et al. (1958) were used for extracting the gonadotrophic activity. The total gonadotrophic activity of the preparations was determined by the mouse uterine weight assay. Although the two extraction methods appeared to be equally efficient, that of Albert et al. was found to produce preparations of higher specific activity and this procedure was adopted for further investigations. The level of activity in the urine of the ovariectomized ewe and of the castrate ram was found to be considerably lower than that found in the urine of post-menopausal or ovariectomized women.

DARSTELLUNG VON GONADOTROPIN AUS MENSCHLICHEN HYPOPHYSEN

ABSTRACT Approximately 3000 human hypophyses were processed by a modification of the method of König &amp; King (1950) in order to obtain potent gonadotrophic extracts. The final product, fraction E3, was found to have a total gonadotrophic activity of 200 HMG U./mg in the mouse uterus test and was 10 times as active as the FSH standard NIH-FSH-S 1 in the HCG augmentation test. MSH, ACTH and LTH contamination was insignificant. The specific activities obtained in other laboratories (Gemzell et al. 1958, 1960; Li 1960; Steelman et al. 1953, 1958, 1959) are not substantially higher. It may therefore be concluded that our relatively simple procedure is just as efficient as the more complicated, time consuming methods referred to above. Furthermore the overall recovery of our method seems to be higher. Attempts were made to obtain a further purification of fraction E3 by means of CMC, Sephadex and DEAE-Sephadex chromatography and also by means of flow-stream electrophoresis. DEAE Sephadex chromatography results in a slight increase in specific activity, which was, however, combined with a substantial overall recovery loss. The other fractionation methods employed gave no satisfactory results. A complete separation of FSH and ICSH activity even by means of CMC chromatography was not obtained. The total gonadotrophic activity per hypophysis was found to be approximately 1000 HMG units (average in unselected batches of hypophyses from various pathology institutes). Estimation in single hypophyses of men and women above the age of 45 resulted in higher values. Single estimations of total gonadotrophin activity in hypophyses of foetuses and of pregnant women have very low values, while in the hypophyses of children no gonadotrophic activity could be detected.

EXPERIMENTAL EXAMINATION OF AN ASSAY FOR URINARY FOLLICLE STIMULATING HORMONE

SUMMARY 1. An assay method for urinary FSH depending on an increase of ovarian weight in mice treated with HCG has been examined experimentally. 2. Synergism was not observed when mixtures were assayed by this method. However, when 'total gonadotrophic activity' was estimated by the weight increase of the mouse uterus there appeared to be some evidence of synergism. 3. The administration of prolactin in total dosages up to 10 i.u./mouse did not interfere with the assay. 4. The addition of oestrogens sometimes affected the assay results and frequently caused a departure from parallelism.

Activité gonadotrope d'un extrait d'urines de femmes en ménopause

An extract from pooled postmenopausal urine has been investigated for its gonadotrophic activity. Dose-response curves have been constructed for its total gonadotrophic activity (stimulation of estrogen secretion as reflected by the uterine weight increase in immature mice) and for its ICSH activity (stimulation of androgen secretion as reflected by the ventral prostate weight increase in hypophysectomised immature rats). In hypophysectomised immature rats, the extract produced repair of the interstitial cells of the testes and complete spermatogenesis. It contains, therefore, FSH as well as ICSH activity in comparable amounts, a fact which opens up interesting therapeutic possibilities.