Ectopic production of human chorionic gonadotropin: A case report

The ectopic production of the β-subunit of human chorionic gonadotropin (hCG) is described in a patient with an anaplastic carcinoma. After chemotherapy the marker decreased in a logarithmic fashion to undetectable levels but the neoplasm progressed and the patient died. The specificity of the β-subunit of hCG is discussed. Discordance of the marker and clinical disease is pointed out, and several possible explanations are outlined. The lack of specificity of the β-subunit of hCG and the discordance that it may exhibit means that its use in diagnosing and following disease progression may be limited.     

Evaluation of PSβ1G and other Tumor Markers in Germ Cell Tumors of the Testis

Pregnancy Specific beta 1 Glycoprotein (PS beta 1G), human choriogonadotropin (hCG), alpha foeto protein (AFP) and Carcino Embryonic Antigen (CEA) were assayed in 58 patients with active germ cell tumors and 20 patients in complete clinical and radiological remission. The markers were negative in all the cases in remission as well as in one case of pure teratoma. The positivity rate of the four markers together is 75%, which is better than for any marker alone. All the markers except AFP seem ubiquitous with respect to the histological classification. The highest positivity rate is obtained for hCG in all the histological types. PS beta 1G is related to hCG but its positivity rate is quite lower. AFP is mainly related to embryonal carcinoma but can be associated with any type of tumor except seminoma. CEA is less frequently positive, always associated with other markers and seems therefore useless for the diagnosis of germ cell tumors.     

Combined Human Chorionic Gonadotropin (HCG) and Human Menopausal Gonadotropin (HMG) Treatment in Gonadotropin-Deficient Males with Pituitary Dwarfism

The effects of hCG-hMG treatment in 13 boys with pituitary dwarfism associated with gonadotropin deficiency, were assessed.
No patients except one showed signs of puberty at a bone age of 13 years or above. The one patient with some signs of puberty did not become fully mature. The hCG-hMG was started at a mean age of 20.4 years. The hCG at a dose of 5,000 IU was injected intramuscularly twice a week and the hMG at a dose of 75 IU was given once a week at first. During treatment, the frequency of hMG injections was increased to twice a week in six patients who still had not produced normal sperm counts. After a mean duration of 19.23 months, spermatozoa appeared in eight patients, of whom four showed more than 20 × 10⁶ sperm/ml. Among six patients who did not have normal sperm counts and had increased hMG injections, one produced a pregnancy and four achieved sperm counts of more than 35 × 10⁶/ml. One patient had refractory azoospermia. In 13 boys with growth hormone and gonadotropin deficiency, hCG-hMG treatment produced normal spermatogenesis in nine patients, one of whom fathered a girl. Thus, hCG-hMG treatment, especially twice-a-week injections of both hCG and hMG, appears to be effective for gonadotropin deficiency in males.     

Effects of cannabinoids on testosterone and protein synthesis in rat testis Leydig cells in vitro.

Various water-insoluble cannabinoids as well as SP-111A, the water-soluble derivative of delta 9-tetrahydrocannabinol (delta 9-THC), reduced hCG and dibutyryl-cAMP stimulated testosterone production by rat testicular Leydig cell preparations. With 0.15 microM (0.05 micrograms/ml) 8-beta-OH-delta 9-THC the inhibition was about 50% of stimulated testosterone synthesis. Dose-related inhibitions were apparent with other cannabinoids and their order of potency in inhibiting stimulated steroidogenesis by the interstitial cells in vitro was found to be: 8-beta-OH-delta 9-THC greater than or equal to 11-OH-delta 9-THC greater than CBN = CBD = CBG greater than or equal delta 9-THC = delta 8-THC. The non-stimulated, basal, steroidogenesis was not affected even with 15 microM cannabinoids. The incorporation of L-[U-14C]leucine into the protein of Leydig cells was markedly reduced by 15 microM cannabinoids under both basal and stimulated conditions. The inhibition of steroidogenesis as well as protein synthesis in rat testicular Leydig cell preparations by various cannabinoids cannot be correlated with their psychoactivity. The present data suggest that cannabinoids at very low concentrations may interfere directly in Leydig cells with both protein and testosterone synthesis, and thus with their function.     

Early effects of hCG on human testicular cyclic AMP content, protein kinase activity, in-vitro progesterone conversion and the serum concentrations of testosterone and oestradiol

Ten infertile men underwent testicular biopsy. Cyclic AMP concentration and cAMP-dependent protein kinase activity were determined in biopsies obtained before, and at 3, 10, 20 and 30 min after an intravenous injection of hCG (1500-5000 IU). The in-vitro conversion of progesterone by testicular tissue, and the serum concentrations of testosterone and oestradiol were then studied before and at 30 min after hCG injection. Intravenous injection of hCG induced a rapid increase in cAMP concentration and in the activity of cAMP-dependent protein kinase. The kinetics of this response indicated that cAMP and cAMP-dependent protein kinase mediate hCG effects on the human testis, presumably via effects on the Leydig cells. No stimulatory effect on steroid conversion in vitro or on the serum concentrations of testosterone and oestradiol were seen after 30 min.     

Treatment with an LHRH agonist or hCG increases interstitial fluid volume and permeability to Evans blue in the mouse testis

Treatment of adult mice with 1 microgram of an LHRH-agonist or with 5 i.u. hCG, subcutaneously, resulted in an increase in the permeability to intravenously injected Evans blue into the testicular interstitial space and in the volume of testicular interstitial fluid. These changes are probably related to an increase in vascular permeability but, in contrast to the situation in rats, this was accompanied neither by an accumulation of polymorphonuclear leucocytes in testicular blood vessels nor by the formation of large inter-endothelial cell gaps in postcapillary venules. The mechanisms mediating the gonadotrophin-induced increase in vascular permeability in the mouse testis thus remain unknown.     

The importance of the Leydig cells in the vascular response to hCG in the rat testis

The increase in permeability of the testicular blood vessels following an injection of hCG into rats is abolished completely if the animals are treated 3 days earlier with ethane dimethane sulphonate (EDS), a compound that effectively eliminates Leydig cells from the testes. As there is other evidence that androgens or prostaglandins are not involved in this vascular response, further studies will be necessary to determine whether these data mean that another vasoactive substance is secreted by the Leydig cells or whether the EDS also eliminates other cells besides the Leydig cells, for example the mast cells found in the vicinity of the testicular artery.     

Hormone binding modified endogenous proteolysis of LH/hCG receptors in rat ovarian plasma membranes

Purified rat ovarian plasma membranes were subjected to incubation under conditions where luteinizing hormone receptors were either free or bound to hCG. When receptor proteolysis was followed by labeling the receptor with tritiated borohydride or [125I]hCG, occupied receptors were found to be more accessible to endogenous proteinases than unoccupied receptors. They exhibited greater rates of degradation and also produced an additional degradation product upon proteolysis. Degradation of other plasma membrane (glyco)polypeptides, however, was not affected by hormone binding. These results indicate that hCG binding induces a conformational or a structural change in its receptor, thereby increasing its susceptibility to endogenous plasma membrane proteinases.     

Male Hypogonadism Associated with Elevated LH, Normal FSH and Low Testosterone Possibly Due to an Abnormal LH Molecule

A male patient of 20 years of age with clinical features of hypogonadism presented high LH, low T and normal FSH blood level. Although the LH data suggested a primary gonadal defect, he responded normally to hCG administration, with a rise of plasma testosterone. During therapeutical administration of hCG he also improved clinically. Thus, the patient's Leydig cells responded to exogenous hCG but not to endogenous LH. This syndrome is likely to be attributable to the presence of an immunologically active but biologically inactive LH molecule.