THE EFFECT OF LOW DOSES OF HUMAN CHORIONIC GONADOTROPHIN ON THE FERTILIZING ABILITY OF HAMSTER EPIDIDYMAL SPERMATOZOA

1973 ◽  
Vol 58 (2) ◽  
pp. 185-192 ◽  
Author(s):  
C. M. LUBICZ-NAWROCKI

SUMMARY The fertilizing ability of spermatozoa in ligated caudae epididymides of golden hamsters was reduced to approximately 25% of the control level after 12 daily s.c. injections of 10 i.u. human chorionic gonadotrophin (HCG), but spermatozoa retained normal fertilizing ability after treatment with higher doses of HCG (30 and 40 i.u./day). This antifertility effect of HCG was mediated through the testes since removal of one testis reduced the adverse effect of 10 i.u. HCG/day by approximately 75% while spermatozoa retained normal fertilizing ability in animals bilaterally castrated and treated with testosterone. Additional experiments revealed that 12 daily injections of 250 μg testosterone significantly reduce fertilizing ability although treatment with 500 μg testosterone daily for the same period had no effect. It was found, also, that the antifertility effect produced by treatment with 10 i.u. HCG daily for 12 days was similar to that after 12 daily injections of 3·5 μg oestradiol benzoate (OB). While 250 μg testosterone/day in combination with OB (3·5 μg/day) augmented the antifertility effect of this hormone, 500 μg testosterone daily prevented to a small but significant extent, the antifertility effects of HCG and OB at these doses. By contrast to their effects on fertilizing ability, testosterone, HCG and OB had no significant effect on seminal vesicular fructose concentration which remained high in each experimental group. It is suggested that the antifertility effect of low doses of HCG results from stimulation of testicular secretion of testosterone and subsequent conversion of limited but significant amounts of testosterone into oestrogens, either in the testis or peripherally, which then antagonize the effects of testosterone in the cauda epididymidis.

1973 ◽  
Vol 58 (2) ◽  
pp. 177-NP ◽  
Author(s):  
C. M. LUBICZ-NAQROCKI ◽  
T. D. GLOVER

SUMMARY Spermatozoa in the ligatured cauda epididymidis of golden hamsters were tested for their fertilizing ability 12 days after hypophysectomy or after hypophysectomy and treatment with testosterone or human chorionic gonadotrophin (HCG). Fertility trials showed that the mean fertilization rate was reduced to approximately 65% of the control level, which contrasts sharply with the previously reported effects of castration, which led to the infertility of spermatozoa within 12 days as a result of androgen withdrawal. The present study showed that loss of fertilizing ability in hypophysectomized animals was also due to a decrease in circulating androgens since treatment with testosterone or HCG (10 or 40 i.u./day) prevented the adverse effect of hypophysectomy. However, there was some indication that sperm survival might also be directly or indirectly dependent, in part, on hypophysial hormones. While daily doses of HCG (10 or 40 i.u./day) maintained fertilizing ability in hypophysectomized animals, treatment with intermediate doses (especially 20 i.u./day) reduced the mean fertilization rate to 40·8%. This paradoxical effect of HCG on sperm survival was shown not to be mediated by the adrenal glands: the magnitude of the effect was related to the amount of testicular tissue present. Thus, when only one testis was present the adverse effect of 20 i.u. HCG/day was reduced by approximately half whereas the spermatozoa retained a high fertilizing ability in animals that were both castrated and hypophysectomized and treated with testosterone. It is suggested that the biphasic effect of HCG is due to the peripheral conversion of limited but significant amounts of circulating testicular androgens into oestrogens which antagonize the effect of testosterone in the epididymis. Attention is drawn to the possibility that specific dose levels of HCG might also be detrimental to sperm survival in the treatment with gonadotrophins of infertility in men.


1975 ◽  
Vol 65 (1) ◽  
pp. 19-25 ◽  
Author(s):  
P. NEAL ◽  
T. G. BAKER ◽  
K. P. McNATTY ◽  
R. J. SCARAMUZZI

SUMMARY The response of mouse ovaries maintained in organ culture to prostaglandin E2 (PGE2) and prostaglandin F2α (F2α) was assessed using quantitative histological and radioimmunoassay procedures. Prostaglandin E2 induced histological changes in the cultured follicles comparable to those induced by human chorionic gonadotrophin (HCG) and the increase in the number of oocytes undergoing preovulatory maturation over the control value was the same irrespective of the treatment (PGE2 alone, HCG alone, or PGE2 + HCG). The amount of progesterone/ ml of culture medium was also significantly higher with these preparations than in control cultures (about 125 ng/ml compared with 57 ng/ml). By contrast, 5 μg PGF2α/ml medium increased neither the number of oocytes undergoing maturation nor the concentration of progesterone in the culture medium. The latter increased when the dose of PGF2α was increased to 30 μg/ml, although the proportion of oocytes beyond the dictyate stage remained at the control level. There was no augmentation in the response (above the level for HCG alone) when HCG and PGF2α were added to the explant medium simultaneously. These results are discussed in terms of the possible mechanism of action of the various preparations.


1975 ◽  
Vol 79 (2) ◽  
pp. 357-365 ◽  
Author(s):  
Karl M. Pirke ◽  
Peter Doerr

ABSTRACT A radioimmunoassay for dihydrotestosterone (DHT) in plasma was developed using an antiserum raised against testosterone-3-oxime-bovine-serum-albumin. After extraction of 1 ml male plasma with diethylether, DHT was separated from testosterone (T) by thin-layer chromatography. A dextran-charcoal-suspension was used for the separation of bound and free ligand. The inter-assay variability was 10.4 % (C. V.) and the detection limit 1.77 ng/100 ml. The accuracy of the method as determined by mass recoveries and the specificity were shown to be satisfactory. Normal values were obtained in 45 young to middle-aged (22–61 years) and 37 old (68–93 years) men. The median and the 95 percentiles were 20.5–51.9–76.3 (ng/100 ml) and 19.5–50.9–101.5 (ng/100 ml) respectively. While DHT did not change in old age T fell by 20.6%. DHT and T showed a significant correlation: rS = 0.426, P < 0.01 (young men), rS = 0.752, P < 0.001 (old men). After 3 daily im injections of 5000 IU human chorionic gonadotrophin (HCG), DHT increased 1.50 times (range: 1.15–2.09, n = 12), T 1.86 times (range: 1.20–2.91, n = 12). After 4 daily administrations of 40 mg fluoxymesterone DHT fell to 29.6% of the control level (range: 16.0–48.2%, n = 12). Blood samples were obtained from a 24 year old man every 15 min for 24 h. A close parallelism was observed between the concentrations of DHT and T in the plasma.


1979 ◽  
Vol 80 (1) ◽  
pp. 83-89 ◽  
Author(s):  
J. R. SOWERS ◽  
A. E. PEKARY ◽  
J. M. HERSHMAN ◽  
M. KANTER ◽  
J. J. DISTEFANO

The immunoreactivity of a commercial preparation of human chorionic gonadotrophin (HCG) was determined in a homologous double antibody radioimmunoassay for HCG using antisera to the β-subunit of the hormone. The immunoreactivity of the commercial HCG was found to be 2·2 ± 0·3 (mean ± 2 s.d.) times the biological potency. Exclusion chromatography of the commercial HCG and then curve resolution of the elution profile derived from the radioimmunoassay revealed that on a molar basis, 21% of the immunoreactivity was attributable to β-HCG. The rate of clearance of this preparation of HCG from the plasma after intravenous administration was determined as a function of the dose administered to ten normal men (age 36–64 years). The doses ranged from 10 000 to 300 000 i.u. immunological potency. The rate of clearance decreased significantly (r = 0·574, P< 0·05) with increasing doses of HCG from a mean of 786 ml/h at the lowest dose to a mean of 298 ml/h at the highest dose. The renal clearance of administered HCG also decreased with increasing doses; the mean renal clearance of the 10 000 i.u. dose was 3·6 times the mean renal clearance after administration of 200 000 i.u. When the accumulated urinary HCG was expressed as a percentage of the dose administered, 14·1% of the 10 000 i.u. dose and 9·8% of the higher doses accumulated in the urine, suggesting that non-renal clearance increased with increasing dose.


1985 ◽  
Vol 107 (1) ◽  
pp. 113-119
Author(s):  
J. Th. J. Uilenbroek ◽  
H. M. A. Meijs-Roelofs ◽  
P. J. A. Woutersen ◽  
P. Kramer ◽  
W. A. van Cappellen ◽  
...  

ABSTRACT To determine whether the decrease in ovarian 5α-reduced androgen production before first ovulation might be caused by an increase in serum LH, prepuberal female rats were injected at 28–31 days of age with low doses of human chorionic gonadotrophin (hCG) (0·05–0·075 i.u., four times daily). This treatment resulted in ovulation of six to ten ova per rat on day 32 in all animals. Treatment with hCG resulted in a gradual decrease in ovarian content and production (i.e. content in ovary and medium after 4 h of incubation) of 5α-dihydrotestosterone (DHT) and 5α-androstane-3α,17β-diol. The ovarian content of DHT and the production of 5α-androstane-3α,17β-diol decreased within 24 h after the first injection of hCG. Oestradiol content and production increased between 24 and 48 h after the start of treatment and was maximal on day 31 (day of pro-oestrus). Activities of 5α-reductase and aromatase were measured in ovarian homogenates obtained on days 29–31. Activity of 5α-reductase in hCG-treated rats was lower than that in control rats on all days studied. Aromatase activity in hCG-treated rats increased between days 29 and 31. It was concluded that multiple injections of low doses of hCG, which may induce ovulation, cause a decrease in 5α-reduced androgen production, which is probably due to a decrease in 5α-reductase activity. The subsequent increase in oestradiol production corresponds with an increase in aromatase activity. The results indicate that the decrease in 5α-reductase activity as observed in ovaries of spontaneously ovulating rats might be caused by the gradual increase in serum LH, which has been found to occur during the last week before first ovulation. J. Endocr. (1985) 107, 113–119


1964 ◽  
Vol 30 (1) ◽  
pp. 87-95 ◽  
Author(s):  
M. X. ZARROW ◽  
K. BROWN-GRANT

SUMMARY The effect of age and dose of a single injection of pregnant mare serum gonadotrophin (PMS) on spontaneous ovulation in immature Wistar rats is described. Ovulation could be induced by human chorionic gonadotrophin (HCG) at least 6 days before it occurred when pregnant mare serum gonadotrophin alone was given. Chlorpromazine was shown to block pregnant mare serum gonadotrophin-induced ovulation at a dose level (0·25 mg. in a 60 g. rat) which has no effect on the ovulatory response to human chorionic gonadotrophin. Higher doses interfered with the action of injected human chorionic gonadotrophin. Ovulation could be induced in the chlorpromazine-blocked animals by the systemic injection of an extract of bovine median eminence, but the sensitivity was too low to use this response for an assay method.


1974 ◽  
Vol 75 (3) ◽  
pp. 617-624 ◽  
Author(s):  
Peter Doerr ◽  
Karl M. Pirke

ABSTRACT The response of plasma oestradiol (Oe2), oestrone (Oe1) and testosterone (T) to stimulation of the Leydig cells with human chorionic gonadotrophin (HCG) and to suppression with a synthetic androgen was ascertained in normal adult males. Three days after daily im injections with 5000 IU HCG, Oe2 increased from 1.93 to 5.66 ng/100 ml (mean of 12 subjects), Oe1 from 2.76 to 4.99 ng/100 ml, and T from 547 to 990 ng/100 ml. Thus, Oe2 increased on the average 3.07 times, Oe1 1.90 times, and T 1.86 times. Four days after oral administration of daily 40 mg fluoxymesterone (9α-fluoro-11β-hydroxy-17α-methyltestosterone), T decreased from 521 to 99.8 ng/100 ml (19.3 % of the control level, mean of 12 subjects), Oe2 from 1.93 to 0.66 ng/100 ml (34.9 % of the control level), and Oe1 from 3.14 to 2.23 ng/100 ml (72.5 % of the control level). Highly significant correlations were found between the pre-stimulation levels of Oe2 and Oe1, between the increments of Oe2 and Oe1 and of Oe2 and T after HCG stimulation.


1989 ◽  
Vol 61 (03) ◽  
pp. 463-467 ◽  
Author(s):  
G M Smith

SummaryIn this study, 5-hydroxytryptamine (5-HT) caused a dose- dependent fall in the circulating platelet count suggesting that 5-HT receptors are activated in rat platelets to cause platelet adhesion and aggregation. When low doses of adenosine diphosphate (ADP) were simultaneously injected with 5-HT, there was a significant potentiation of the responses to ADR Ketanserin significantly reduced the potentiated responses. When higher doses of ADP were infused with bolus injections of 5-HT there was no potentiation and ketanserin did not reduce these responses. Ketanserin did not inhibit the collagen-induced fall in circulating platelet count, but did significantly increase the rate of return to the basal platelet count compared with control. 5-HT did not cause a fall in platelet count in guinea-pigs


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