Human Pituitary Gonadotropin Research Articles

Total gonadotropins and follicle-stimulating and luteinizing action of human pituitary gonadotropin

Total gonadotropins and follicle-stimulating and luteinizing action of human pituitary gonadotropin

MOLECULAR WEIGHT OF HUMAN PITUITARY GONADOPTROPINS AS DETERMINED BY RADIATION INACTIVATION OF BIOLOGICAL ACTIVITY.

Purification is not required to determine the molecular weight of protein hormones by means of radiation inactivation. Acetone-dried human pituitary powder, a urinary preparation from human castrate males (NIH-HPG-UE), and a urinary preparation from postmenopausal human females (Pergonal) were radiated with 2.0 mev electrons at varying doses. Loss of biological activity was measured by means of prostate and testes weight in hypophysectomized rats. When the loss of biological activity was plotted against radiation dose, exponential curves were obtained. These plots were identical for all 3 gonadotropin preparations and for each of the bio-assays. Molecular weight estimates of the gonadotropins in all 3 preparations were similar and averaged 31.4 × 103 (range 30.0–34.0), irrespective of which bioassay was used. Using identical methods, previous studies on human chorionic onadotropin have also resulted in molecular weight estimates of 30.4 × 103. It is concluded that human FSH, LH and chorionic gonadotropin have similar molecular weights of approximately 30,000.

EFFECTS OF HUMAN MENOPAUSAL GONADOTROPHIN PREPARATIONS IN DIFFERENT BIOASSAY METHODS

ABSTRACT Several gonadotrophin preparations, HMG (Human Menopausal Gonadotrophin), HPG (Human Pituitary Gonadotrophin) and NIH FSH S1 (a FSH preparation distributed by the National Institute of Health) were investigated for biological activity, using three methods of assay. The rat augmentation test, specific for FSH, and the rat seminal vesicle weight test, specific for ICSH both gave statistically valid results. The potencies were expressed in terms of the IRP (International Reference Preparation for HMG), and the International HCG Standard respectively. The gonadotrophic activity as determined by the rat uterine weight method was expressed in terms of IRP and in terms of the International HCG Standard. Good agreement was found between the results in the uterine weight method and the seminal vesicle test, suggesting a strong ICSH dependence for the former. On the other hand, the results of the uterine weight method and the augmentation test were not in agreement. Consequently the rat uterine weight method must be regarded as completely unsuitable for the assay of FSH-activity. Among the three test methods studied, the augmentation test appears to be the only one suitable for the assay of the FSH content of gonadotrophin preparations for clinical use. Fractionation of HMG with ethanol led to preparations with high FSH activity, 200 to 300 times that of IRP, but with little ICSH activity. Most of the ICSH was concentrated in other fractions, indicating that both hormones can be separated. In starch gel electrophoresis these fractions showed different patterns.

IMMUNOLOGIC CROSS-REACTION BETWEEN HUMAN CHORIONIC GONADOTROPIN AND HUMAN PITUITARY GONADOTROPIN.

The capacity of human pituitary gonadotropin (NIH-HPG-UE) to absorb antibodies to HCG was measured in 7 experiments utilizing 2 rabbit and 1 sheep anti-HCG preparations. Maximum estimates of the degree of immunologic cross-reaction between NIH-HPG-UE and HCG varied from 34 to 87 % for the different antisera. One minimum estimate was 38%. An “LH-poor” NIHHPG- UE was able to neutralize only 18% of anti-HCG activity. Immunodiffusion in agar gel demonstrated a reaction of partial identity between HCG and LH. It was concluded that a partial immunologic cross-reaction between HPG and HCG exists and that LH is the component of HPG mainly responsible for the cross-reaction. (Endocrinology 75: 352, 1964)

LUTEINIZING HORMONE ACTIVITY OF HUMAN PITUITARY GONADOTROPIN AS DETERMINED BY THE VENTRAL PROSTATE WEIGHT AND THE OVARIAN ASCORBIC ACID DEPLETION METHODS OF ASSAY.

The luteinizing hormone (LH) activity of 3 preparations of human pituitary gonadotropin (HPG) made from postmenopausal urine, of 1 HPG preparation made from male urine and of 1 HPG preparation made from the urine of eunuchs was determined by 2 assay systems: the ovarian ascorbic acid depletion (OAAD) method and the ventral prostate weight (VPW) method with ovine NIH-LH-S1 as standard. It was found that the VPW method indicated the presence of 12 times more LH activity in the 5 HPG preparations than did the OAAD method. In the search for an explanation for this discrepancy, the OAAD and the VPW methods for assay of LH activity were analyzed with respect to sensitivity, accuracy and interference by other hormones. Consideration also was given to the relationship of the 2 bio-assay systems to the chemical and physical nature of the preparations and to the effect of over-all rate of metabolism of the hormone. It was concluded that: 1) the discrepancy in LH estimation by the 2 assay systems employed was probab...

FURTHER OBSERVATIONS ON THE IMMUNOLOGICAL BEHAVIOUR OF HUMAN PITUITARY AND CHORIONIC GONADOTROPHINS.

SUMMARY Antisera were raised to human chorionic gonadotrophin (HCG) and human menopausal gonadotrophin (HMG). Normal human serum and human pituitary and chorionic gonadotrophins reacted with both antisera in immunological experiments. After absorption with human serum, the γ-globulin fractions of the antisera were isolated, and only the reaction to the hormone preparations remained. Immunoelectrophoresis revealed a common antigenic factor in the α2-β globulin region. The γ-globulin fraction of HCG antiserum seems to be suitable for the assay of HCG, while that of the HMG antiserum might be employed for the detection of HMG.

INCIDENCE AND RATE OF APPEARANCE AND DISAPPEARANCE OF ANTIGONADOTROPHIN IN THE BLOOD OF PATIENTS TREATED WITH PREGNANT MARES' SERUM GONADOTROPHIN

ABSTRACT Thirty-eight patients with amenorrhoea were treated with repeated series of injections of pregnant mares' serum gonadotrophin + human chorionic gonadotrophin. Each course consisted of 5 injections of 1500 IU or 3000 IU of serum gonadotrophin, Antex®, followed by 3 injections of 1500 IU or 3000 IU of chorionic gonadotrophin, Physex®, If required, this treatment was repeated at a few months' intervals, in some cases up to 5 times. After each course, the blood was studied for the presence of antigonadotrophin to Antex. Blood specimens were drawn in all cases 21 days after the last injection of Antex. Antigonadotrophin was found to be present in one out of 15 patients after the 1st course, in 8 out of 20 after the 2nd course, in 13 of 16 after the 3rd, and in 6 of 6 patients after the 4th and 5th courses. Progonadotrophic activity was demonstrated in the blood of 6 patients after the 1st course, in 4 after the 2nd course, and in one on the 10th day after the 3rd course. In 6 cases blood samples were obtained also immediately before, during and immediately after the treatment. Three showed, during the 3rd, 4th and 5th course respectively, antigonadotrophin in the blood even before the last injection of Antex. These courses were ineffective, and no patient got menstrual bleeding as a result of the 4th or 5th course. Some patients developed bleeding after the 3rd treatment, although antigonadotrophin was demonstrated in the blood on the 21st day. In these cases the antigonadotrophin presumably did not form until the injections of Antex had exerted their effect. The antigonadotrophin occurring during these therapeutic courses inactivates only serum gonadotrophin and limits effective treatment by this gonadotrophin to about 4 weeks in continuous therapy and to 3 of the brief, intensive courses employed in the present series. Apart from this, the formation of this antigonadotrophin did not have harmful consequences. It disappears from the blood within a period of a few months, occasionally up to about a year, and it does not prevent subsequent treatment with human pituitary gonadotrophin from being effective.

THE TREATMENT OF ANOVULATION BY HUMAN PITUITARY GONADOTROPHIN.

THE TREATMENT OF ANOVULATION BY HUMAN PITUITARY GONADOTROPHIN.

Preparation of Highly Potent Human Pituitary Gonadotrophins.

SummaryHuman FSH and LH fractions, equal in potency to any previously reported, have been further purified by gel filtration and ion-exchange chromatography. The most potent of these new fractions was 94 times more active than NIH-FSH-S1 and 2.9 times more active than NIH-LH-S1, respectively.The writers are indebted to Jean Batchelder, Lynn Crook, and Karin Westphal for skilled technical assistance, to Professors G. A. Brecher and A. E. Wilhelmi for critical reading of the manuscript, and to Endocrinology Study Section, N.I.H., for supplies of XIH-LH-S1 and NIH-FSH-S1.

Further evidence for an ovarian source of urinary pregnanetriol.

ABSTRACT Urinary steroid excretion and vaginal cytology were studied in a 31-year old adrenalectomised female during and after the administration of human pituitary gonadotrophin (with predominantly F.S.H. activity), and corticotrophin. A significant increase (to about 4 times the basal values) in the daily output of 17β-oestradiol, oestrone, oestriol, pregnanediol and pregnanetriol was observed with gonadotrophin injection and a withdrawal bleeding occurred four days after the end of the ovarian stimulation. These observations are added proof of the existence of an ovarian precursor for pregnanetriol (5β-pregnane-3α,17α,20α-triol).

Qualitative studies of the urinary gonadotropin excretion of twenty patients in remission from choriocarcinoma and related trophoblastic diseases.

The urinary extracts from 20 patients in complete remission from choriocarcinoma and related trophoblastic diseases were studied retrospectively in order to test the possibility of differentiating human chorionic gonadotropin (HCG) from human pituitary gonadotropin (HPG) by bio-assay. The urines were extracted and concentrated by the kaolin-acetone technique, and assayed by the response of the testes and ventral prostate of immature hypophysectomized male rats to graded doses of the extract. The testis weights obtained by doses which produced ventral prostate weights of 25 mg (VP25) were compared for 2 urine specimens from each patient, one collected when the tumor was active and another when the patient was in clinical remission. In 17 out of 20 cases, the testis weights at VP25 of the post-remission urine were higher than those of the preremission urine. These differences were more striking among oophorectomized patients than among those with intact ovaries, but were statistically significant in both gr...

The effect of derivatives of dithiocarbamoylhydrazine on hormone excretion in postmenopausal women.

SUMMARY Estimations of human pituitary gonadotrophins (HPG), total 17-hydroxycorticosteroids, total 17-oxosteroids and oestrogens have been performed in seven hospitalized postmenopausal subjects receiving treatment with the dithiocarbamoylhydrazine derivatives Compound 22365 and Compound 33828 (Imperial Chemical Industries Ltd.). Both compounds were shown to be inhibitors of pituitary gonadotrophic function as indicated by urinary HPG assays; Compound 33828 was more active in this respect than Compound 22365. When Compound 22365 was administered to individual subjects at two different dose levels the time taken for urinary HPG levels to return to pretreatment values was longer in the case of the higher dose. Neither of the compounds studied produced any effect on adrenocortical function as judged by urinary assays of 17-hydroxycorticosteroids, 17-oxosteroids and oestrogens. Side effects were noted in two of the seven patients studied. In one subject with pre-existing liver damage it was necessary to stop treatment with Compound 22365 because of the development of mild jaundice.

Purification of pituitary gonadotropin from urine of eunuchs.

ABSTRACT Human pituitary gonadotropin (HPG) from the urine of eunuchs was purified in 3 stages. The HPG was adsorbed by kaolin, eluted with ammonia and precipitated in 66% acetone. HPG was extracted from the precipitate with 70% ethanol containing 10% ammonium acetate and prepared in dry form by precipitation in 90% ethanol. Further impurities were removed by adsorption onto diethylaminoethyl cellulose in 0.05 M phosphate buffer. The mean purification achieved was 78- fold, with a mean retention of 37% of the original activity. The purified product was 140 times stronger than the unofficial standard HMG-20A prepared from postmenopausal urine.

Performance control of preparations which could be used as reference material for the estimation of urinary gonadotropins in the mouse uterine weight method.

ABSTRACT The performance of 3 human pituitary gonadotropin (HPG) extracts obtained from the urine of postmenopausal women (PM, Pergonal 22-C and Pergonal 23) and of estrone was investigated in the mouse weight assay. A number of assays were conducted over a 2-yr period. HPG extracts were assayed alone, against each other and/or simultaneously with estrone. No significant difference in animal sensitivity was observed over a long period of time with any of the preparations used. However, there was a change in slope positions in assays conducted with Pergonal 22-C and PM in 1961 as compared with 1960. When HPG preparations were tested against each other on several occasions, close agreement of relative potency (RP) values was observed. The estimated RP's were homogeneous, as judged by the variance ratio: F (P) >0.05. PM was demononstrated to maintain its potency when stored in the dry powdered form over a 2-year period. Similarly, a frozen “stock” solution of Pergonal 22-C was demonstrated to maintain its po...

Chromatography on diethylaminoethyl-cellulose of human and ovine urinary pituitary gonadotrophins

Chromatography on diethylaminoethyl-cellulose of human and ovine urinary pituitary gonadotrophins

EFFECTS OF HUMAN PITUITARY GONADOTROPHIN (HPG) IN HYPOGONADOTROPHIC OVARIAN INSUFFICIENCY

Journal Article EFFECTS OF HUMAN PITUITARY GONADOTROPHIN (HPG) IN HYPOGONADOTROPHIC OVARIAN INSUFFICIENCY This work was supported by a grant from the Deutsche Forschungsgemeinschaft. Get access G Bettendorf, G Bettendorf Universitätsfrauenklinik, Hamburg-Eppendorf, Germany Search for other works by this author on: Oxford Academic Google Scholar D Ahrens D Ahrens Universitätsfrauenklinik, Hamburg-Eppendorf, Germany Search for other works by this author on: Oxford Academic Google Scholar Acta Endocrinologica (Norway), Volume 40, Issue 3_Supplement, Aug 1962, Page S133, https://doi.org/10.1530/acta.0.040S133 Published: 01 August 1962

Induction of Ovulation with Human Pituitary Gonadotrophins

Induction of Ovulation with Human Pituitary Gonadotrophins

Book Review: Human Pituitary Gonadotropins

Book Review: Human Pituitary Gonadotropins

Studies on human urinary and pituitary gonadotrophins.

Studies on human urinary and pituitary gonadotrophins.

Purification of pituitary gonadotropin from urine of postmenopausal women.

Human pituitary gonadotropin (HPG) from the urine of postmenopausal women was purified in three stages. After preliminary filtration of the urine with celite, HPG was adsorbed by kaolin, eluted with ammonia and precipitated by 66 per cent acetone. HPG was extracted from the precipitate by 70 per cent ethanol containing 10 per cent ammonium acetate and was prepared in a dry form by precipitation with 90 per cent ethanol. Further impurities were removed by adsorption onto diethylaminoethyl cellulose in 0.05M phosphate buffer. The mean purification achieved was 35-fold, with retention of 56 per cent of the original activity. No alteration in the proportions of follicle-stimulating and luteinizing activity of the purified product, as compared with the crude concentrate, was detected. The purified product was 86 times stronger than the unofficial standard HMG-20A, also prepared from postmenopausal urine.