Activity Of Human Chorionic Gonadotropin Research Articles

Serum human chorionic gonadotropin, human chorionic somatomammotropin, and progesterone following intra-amniotic injection of hypertonic urea

Serum human chorionic gonadotropin (HCG), human chorionic somatomammotropin (HCS), and progesterone were determined sequentially by radioimmunoassay in 7 patients following mid-trimester intra-amniotic instillation of hypertonic urea. A steady decline in serum HCG activity was noted throughout the entire induction-abortion interval in each patient. In contrast, HCS and progesterone did not decrease significantly until the onset of clinical labor, at which time both hormones declined rapidly and at similar rates. The possible significance of these results is discussed.

The effect of corticotrophin on the rat uterine weight response to human chorionic gonadotrophin.

ABSTRACT The activity of human chorionic gonadotrophin (HCG) in the mouse uterus assay is augmented by the daily injection of corticotrophin (ACTH). This phenomenon has been further investigated in the rat. Synthetic ACTH (75μg) and dehydroepiandrosterone (1.0 mg) augmented responses to 0.1 IU, 0.2 IU and 0.4 IU HCG in the rat uterus assay. The basal uterine weight was also elevated by the treatment. This effect could not be demonstrated in castrated or hypophysectomised animals, and in the latter the response to HCG was not augmented. Cortisone and corticosterone did not affect HCG assay. Cortisone administration did not suppress the augmenting effect of either carbon tetrachloride or urine extract administration on HCG activity. Mean uterine weights from bilaterally adrenalectomised rats were significantly higher than those from intact or sham operated animals. The results are discussed with reference to the augmentation of HCG activity produced by non-specific stressful procedures.

Studies on a neuraminidase containing gonadotropin inhibitor substance in bovine pituitary extracts.

Fractions derived from whole bovine pituitary glands or bovine anterior lobes were found to inhibit the ovarian weight-gain activity of mixtures of ovine follicle stimulating hormone (FSH) and human chorionic gonadotropin (HCG), bovine FSH and HCG, or HCG alone. These fractions also inhibited the ovarian ascorbic acid depleting (OAAD) activity of HCG but not bovine luteinizing hormone (LH). Such effects were seen only when the gonadotropin inhibiting (GI) fraction was mixed with the gonadotropin prior to bioassay. Separate site injections of GI and gonadotropin abolished the inhibitory response. GI failed to inhibit endogenous secretions of gonadotropins in normal cycling female rats, as reflected by ovarian and uterine weights, ovarian histology and vaginal smear patterns. FSH and HCG, but not bovine LH, have been reported to require sialic acid for biologic activity. GI was shown to exhibit neuraminidase activity over a wide pH range. Because of this, it is suggested that a neuraminidase-like enzyme may...

Immunochemical studies on human chorionic gonadotropin (HCG). I. Characterization of HCG.

Human chorionic gonadotropin (HCG) with a biological potency of 19,000 IU/mg has been obtained by a combination of procedures involving gel filtration on Sephadex G-100 and chromatography on SE cellulose. However, these biologically active preparations are not immunochemically pure. A component of serum was always present and at times a component of urine was also detected; neither were associated with pregnancy. Amino acid and amino sugar analyses were determined on three partially purified materials of different biological potencies and the significant changes are noted in the text. Reduction of HCG preparations with 2-mercaptoethanol destroyed both biological and immunological activity of HCG but did not affect the immunological activity of the extraneous serum and urinary components. Chymotrypsin treatment of a purified fraction of the hormone drastically altered the immunoelectrophoretic properties of HCG, but had little effect on the ability of the material to inhibit agglutination. Fractionation of a sample of the purified material on Sephadex G-100 after enzyme digestion did not aid in the isolation of immunologically reactive, homogeneous material.

Gonadotrophin inhibitory properties of pineal extracts.

EXTRACTS of urine and pineal are capable of inhibiting the activity of human chorionic gonadotrophin (HCG) in the mouse uterus assay1,2. The failure to detect an inhibitor in urine from patients with sexual precocity due to pinealoma suggested that the pineal was the source of the urinary gonadotrophin inhibitor1. On the other hand, the presence of a gonadotrophin inhibitor in the pineal or in urine has been doubted3,4 or the effects of the latter have been ascribed to the toxicity of the extracts used5. The gonadotrophin inhibitory properties of pineal extracts clearly warrant further investigation and I report here the effects of a pineal extract on gonadotrophin responses in the mouse uterus assay.

Effect of toxic urinary extracts on specific assays for human chorionic gonadotrophin and follicle-stimulating hormone.

ABSTRACT Boiled urinary extracts, which had inhibited the activity of human chorionic gonadotrophin (HCG) in the mouse uterus assay, potentiated the effects of HCG and follicle-stimulating hormone (FSH) in the ovarian ascorbic acid depletion and rat ovarian augmentation assays respectively. This treatment inhibited responses to FSH when the ovarian augmentation assay was conducted in hypophysectomised animals. A toxic urinary extract did not affect the activity of HCG in the ventral prostate weight assay in either intact or hypophysectomised rats. Reasons for the different effects of boiled urinary extracts in these assays are discussed.

Effect of 5-methoxytryptophol and melatonin on uterine weight responses to human chorionic gonadotrophin.

Boiled urinary extracts inhibit the activity of 0·4 i.u. human chorionic gonadotrophin (HCG) in the mouse uterus assay (Hipkin, 1967) and a pineal source for this urinary gonadotrophin inhibitor has been suggested (Soffer, Fogel & Rudavsky, 1965). In intact rats, boiled urinary extracts augment the activity of small doses of HCG but this effect disappears when the animals are hypophysectomized (Hipkin 1970). Two pineal substances, melatonin and 5-methoxytryptophol, inhibit gonadal function (Mclsaac, Taborsky & Farrell, 1964). These materials have therefore been tested for their effects on HCG activity to determine whether they have the same properties as the urinary factor. Animals were obtained from colonies bred at the Statens Seruminstitut. The doses of HCG and the experimental procedures were the same as those used previously (Hipkin, 1967, 1970), but instead of boiled urinary material, daily s.c. injections (0·2 ml each) of 5-methoxytryptophol or melatonin (20 μg to mice, 200 μg to rats)

The effect of alterations in adrenocortical function on the mouse uterine weight response to human chorionic gonadotrophin.

ABSTRACT The activity of human chorionic gonadotrophin (HCG) in the mouse uterus assay depends on the secretion of endogenous gonadotrophin. This source of gonadotrophin is suppressed when the animals are starved or injected with toxic substances, and the response to HCG is therefore inhibited. There is good evidence that this is the mode of action of the urinary gonadotrophin inhibitor (GIM). Since it has been claimed that stress-induced inhibition of gonadotrophin secretion is related to alterations in adrenocortical function, the present investigation is concerned with the response to HCG in animals with experimental hyper- and hypoadrenocorticalism. ACTH gel (300 mU) and a depot form of synthetic ACTH (15 μg) augmented the uterine weight response to HCG (0.5 IU). Normal responses were obtained in animals treated with HCG and either cortisol (300 μg), corticosterone (300 μg) or dehydroepiandrosterone (300 μg). Bilateral adrenalectomy produced similar effects to those previously described for GIM and stressful stimuli, namely, inhibition of HCG activity but no impairment of the responses to follicle-stimulating hormone (FSH), HCG given with FSH, or oestrone. It was thought that these results were produced by the metabolic and traumatic effects of the operation rather than by increased secretion of ACTH per se. Cortisol, corticosterone and ACTH gel did not influence the effect of GIM on HCG activity in the mouse uterus assay. The results suggest that suppression of endogenous gonadotrophin secretion following acute stress is not secondary to increased secretion of ACTH or hyperfunction of the adrenal cortex.

Follicle-stimulating activity of human chorionic gonadotropin.

Journal Article Follicle-Stimulating Activity of Human Chorionic Gonadotropin Get access A. ALBERT A. ALBERT 1Section of Endocrine Research, Mayo Clinic and Mayo Graduate School of Medicine Rochester, Minnesota 55901 Search for other works by this author on: Oxford Academic Google Scholar The Journal of Clinical Endocrinology & Metabolism, Volume 29, Issue 11, 1 November 1969, Pages 1504–1509, https://doi.org/10.1210/jcem-29-11-1504 Published: 01 November 1969 Article history Received: 18 June 1969 Published: 01 November 1969

Follicle stimulating hormone-like activity in human chorionic gonadotrophin preparations.

ABSTRACT The follicle stimulating hormone (FSH)-like activity of human chorionic gonadotrophin (HCG) preparations was assayed by the method based on the ovarian weight augmentation in intact immature rats. The potencies ranged from 4.8 to 7.4 IU equivalents of FSH per mg. The FSH-like potency of the Second International Standard Preparation of HCG was 8.5 IU per vial. However, when in intact immature rats the ovarian weight response to HCG preparations was compared at a wide range of doses (40 to 51 200 IU) to that obtained with a human menopausal gonadotrophin (HMG) preparation (0.5 to 128 IU of FSH) in the presence of 40 IU of HCG, significant differences were found. The assays conducted in hypophysectomised immature female rats were invalid, because of lack of parallelism. Antisera were prepared by immunising rabbits with HCG and human hypophysial gonadotrophin (HHG) preparations and the antigonadotrophin profiles (HCG-, FSH- and FSH-like neutralising potencies) of these antisera were established by the use of statistically valid bioassay procedures. The anti-HCG and anti-HHG sera neutralised the FSH activity of HMG preparations as well as the FSH-like activity of HCG preparations. However, 3 to 175 times more antiserum was required to neutralise the equivalent of 1.0 IU of FSH-like activity present in HCG than expected on the basis of the anti-FSH potency of the antisera. On the other hand, there was a high degree of correlation between the neutralising potencies of the antisera when tested against the FSH-like activity and the HCG activity of various HCG preparations. When the FSH-like activity of an HCG preparation was quantitatively neutralised with an anti-HCG serum, some 30 per cent of the HCG activity remained unneutralised, as evidenced by repeated bioassays. Although at least 2000 IU of this »FSH-free« HCG was administered to groups of intact as well as hypophysectomised immature female rats, this high dose of HCG did not induce an increase in ovarian weight beyond that elicited by 40 IU of untreated HCG. Histological examination of the ovaries indicated lack of follicle stimulation in the hypophysectomised, but not in the intact immature animals. There was an excessive stimulation of the interstitial cells in both types of animals. The data indicate that the FSH-like activity of HCG preparations is neither due to a contamination by FSH of pituitary origin, nor is it an evenly distributed intrinsic property of the HCG molecules. It is also concluded that the gonadotrophic activity of biologically pure HCG in immature hypophysectomised female rats consists of a specific stimulation of the interstitial cell apparatus. Such HCG preparations do not induce any follicle stimulation, not even when administered in excessive doses.

Selective inhibition of the follicle-stimulating and luteinizing principles in the gonadotropic hormones of different species

The effect of hydrogen peroxide (H 2O 2) and heat treatment has been studied as affecting the biological activity and the immunological specificity of the gonadotropins of three species. The hormones studied were human chorionic gonadotropin (HCG), human menopausal gonadotropin (HMG), pregnant mare serum gonadotropin (PMSG), follicle-stimulating and luteinizing hormones (FSH and LH) of human and ovine origin. The results indicated that heating at 100° for 30 min completely destroyed the follicle-stimulating (FS) activity present in HCG, HMG, and human and ovine FSH. The FS principle in PMSG was destroyed at 70° and the LH activity at 100°. Human and ovine LH were not significantly affected by this treatment. The immunological activity of the follicle stimulating principle present in HCG, HMG, and human FSH was completely destroyed on heating the hormones at 100° whereas the luteinizing principle in HCG, human LH, and PMSG was only partially affected. The activities of both ovine FSH and LH remained unaffected. Treatment with 30% hydrogen peroxide for 1 hour at room temperature destroyed completely the biological activity of the luteinizing principle in HCG and HMG, human LH, and ovine FSH. The luteinizing principle in ovine LH was partially destroyed by this treatment, but the follicle-stimulating activity of human FSH, HCG, and HMG remained unaffected. Treatment with 30% hydrogen peroxide failed to destroy the immunological activity of human and ovine FSH and ovine LH, but completely destroyed the LH activity present in HCG, HMG, and human LH. The follicle-stimulating principle in gonadotropins of the human species is inactivated when the hormones are heated at 100° for 30 min whereas the LH principle is destroyed by treatment with 30% hydrogen peroxide. There is, however, a difference in the selective inactivation of the follicle-stimulating and luteinizing principles of gonadotropins of the other species studied in spite of the similarity in their biological actions.

Pregnancy in the rabbit following immunization with human chorionic gonadotropin

Antibodies to gonadotropins may inhibit the biologic activity of the same or closely related gonadotropins. Rabbits immunized with human chorionic gonadotropin (HCG) formed agglutinating antibodies to the HCG. The immune serum inhibited the biologic activity of HCG. However, the immunized rabbits ovulated and became pregnant despite the circulating antibodies. This suggests that there is no cross reaction between HCG and rabbit gonadotropin.

DISSOCIATION OF IMMUNOLOGICALLY AND BIOLOGICALLY ACTIVE HUMAN CHORIONIC GONADOTROPIN FROM THE SPECIFIC PRECIPITATE

It has been questioned whether the human chorionic gonadotropin (HCG) could form the specific precipitate with its antiserum or not. To clarify this point directly, the absorbed rabbit anti-HCG serum which showed only one precipitin band to HCG preparation and no band to human serum or child urine protein, was incubated with partially purified HCG at 37°C for 60 minutes and then refrigerated at 4°C for four days. The resulting precipitate was completely washed until no HCG activity was shown in the supernatant and placed in glycine-HCl buffer (pH2.5, 0.167M), and then passed through a Sephadex G-100. The immunologically and biologically active HCG was dissociated from the specific precipitate and fractionated apart from the rabbit 7Sr-globulin. This result was a direct proof that HCG could produce the precipitating antibody in immunized rabbit.

THE INFLUENCE OF HUMAN SERUM ON THE ACTIVITY OF HUMAN CHORIONIC GONADOTROPHIN IN MALE RANA RIDIBUNDA.

SUMMARY The effect of human serum as vehicle in the bioassay of human chorionic gonadotrophin (HCG) has been investigated in male Rana ridibunda. It was shown that undiluted serum may depress or increase the activity of HCG, while diluted serum may have no influence on the activity. The influence of the serum depends on the time lapse between the administration of the hormone and the measurement of its effect in the test animal, as well as on the dilution of the serum. In the light of the results presented, it is suggested that when serum HCG is assayed in male R. ridibunda, the standard preparation of HCG should be dissolved in serum and the frogs should be examined for spermiation 5 and 12 hr. after the injection. If, however, the standard preparation is dissolved in saline, only diluted serum should be used in the test.

IMMUNOLOGICAL CROSS REACTIONS AMONG GONADOTROPHINS.

ABSTRACT Immunological cross reactions among the three gonadotrophins, ovine interstitial cell-stimulating hormone (ICSH), pregnant mare serum gonadotrophin (PMSG) and human chorionic gonadotrophin (HCG) have been investigated. The earlier findings in this laboratory that rabbit antiserum to ICSH inhibited the biological activity of PMSG was confirmed. Antiserum to PMSG was found to inhibit ICSH. The biological activity of HCG in hypophysectomized female rats was not inhibited by antiserum to either ICSH or PMSG in these experiments, but other evidence shows that antiserum to ICSH is sufficiently high doses does inhibit the biological effects of HCG. Both PMSG and HCG showed precipitin reactions with antiserum to ICSH, the amounts of protein precipitated being much less than when ICSH was used. No precipitate was formed when ICSH or HCG was added to antiserum to PMSG. The antiserum to PMSG contained antibodies to the horse serum proteins that were present as contaminants of the PMSG. These were partly absorbed with horse serum without loss of the anti-PMSG activity.

RADIATION INACTIVATION OF THE IMMUNOLOGICAL AND BIOLOGICAL ACTIVITIES OF HUMAN CHORIONIC GONADOTROPIN.

RADIATION of protein hormones or enzymes results in loss of activity. The rate of inactivation can be used to estimate the volume and weight of the active portion of the molecule if this rate is exponentially related to the dose of ionizing radiation and low-density ionizing radiation is used1. Previous investigations2 have demonstrated that the rate of loss of hormonal activity of human chorionic gonadotropin (HCG) exposed to a 2.0-MeV electron beam was exponential and was identical when measured by four bioassays: in intact immature rats by (1) uterine weight, and (2) ovarian hyperaemia responses; in hypophysectomized rats by (3) testes, and (4) prostate weight responses.

Immunologic studies on gonadotropins: II. Biological assessment of the antigenic nature of the follicle-stimulating principle in human chorionic gonadotropin preparations.

The nature of the folliclestimulating principle in human chorionic gonadotropin preparations was studied by combining both immunologic and bio-assay techniques. Biological assays for human urinary menopausal gonadotropin (HMG) and human chorionic gonadotropin (HCG) were carried out in immature mice, each in the presence of antisera to both antigens. Antiserum to HMG neutralized follicle-stimulating activity of both the HMG and HCG preparations, without affecting the HCG activity of the HCG preparation. Antiserum to HCG neutralized HCG activity and also that follicle-stimulating activity which was contained in the HCG preparations. Results indicate that the follicle-stimulating principle found in preparations of HCG is similar to the follicle-stimulating principle found in HMG.

An immunochemical study of sheep pituitary interstitial cell-stimulating hormone

Rabbit antiserum to highly purified interstitial cell-stimulating hormones (ICSH) from sheep pituitary glands ( β s-ICSH) has been produced. Various immunochemical studies indicated that β s-ICSH is a homogeneous protein. This antiserum was shown to form precipitable antibody-antigen complexes in crude extracts of rat and pig pituitaries. Injections of the antiserum into normal rats were found to inhibit the endogenous ICSH activity. Bioassay in either normal or hypophysectomized rats showed that the antiserum to β s-ICSH inhibits not only the activity of sheep ICSH but also that of pregnant mare serum gonadotropin and human ICSH. The ICSH activity of crude extracts of whale, pig, and rat pituitaries can be counteracted by simultaneous injections of the rabbit β s-ICSH antiserum, whereas the ICSH activity of human chorionic gonadotropin and chicken pituitary extract was not neutralized by the antiserum.