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  • Author: I. I. GESCHWIND x
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D. L. Mednick, M. S. Barkley and I.I. Geschwind

Summary. Pregnant mice were treated with antiserum to LH or bromocriptine to inhibit the activity of LH and prolactin, respectively. Luteal function was monitored by the radioimmunoassay of plasma progesterone. Bromocriptine treatment on Days 2 or 5 of pregnancy produced a rapid decrease in progesterone secretion, but had no effect on luteal function when given on Days 6, 7 or 8 of gestation. Treatment with LH antiserum before implantation did not inhibit progesterone secretion, but luteal function was severely impaired when the antiserum was given on Days 5–9 of pregnancy. These results demonstrate the dynamic nature of luteal dependency on prolactin and LH, and indicate that LH is an essential component of the luteotrophic complex of the mouse.

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Concentrations of plasma LH and FSH were measured by radioimmunoassay in four strains of mice maintained in controlled lighting. Gonadotrophin levels in an unselected control line (Line C) were measured under the following conditions: induced cycles; spontaneous cycles; cycles in absence of males and post-partum cycles. In mice with induced cycles, LH reached a mean of about 40 ng/ml between 16.00 and 17.00 hours of pro-oestrus. Levels of FSH reached a peak of around 2800 ng/ml about 2 hr later, between 19.00 and 20.00 hours, suggesting that the function of FSH is to stimulate growth of the crop of follicles which will ovulate during the succeeding oestrous cycle. Spontaneously cycling mice of Line C also had a mean LH concentration of about 40 ng/ml, but this peak began 1 hr later at 17.00 hours of pro-oestrus and persisted for about 4 hr. No well-defined FSH peak was found. Only two of seventy individually caged females killed during pro-oestrus had LH or FSH levels greater than the mean di-oestrous levels in induced and spontaneously cycling animals. Within 24 hr of parturition, there was no one time when the majority of mice showed elevated levels of LH or FSH. The timing and magnitude of gonadotrophin release during pro-oestrus of induced cycles in lines successfully selected for small litter size, high embryo survival, and high ovulation rate were the same as for Line C, suggesting that the principal effect of selection was probably to alter the sensitivity of the target organs.

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The gonadotrophic activity of sera from two mares treated either with human chorionic gonadotrophin or with crude ovine pituitary fsh as antigens has been studied in intact and hypophysectomized immature female and male rats. The studies were projected over a 4-year period during which time the mares were subjected to three and four sequences of immunization, respectively.

One-third millilitre of serum from the mare treated with ovine fsh increases ovarian and uterine weights in intact immature female rats, while 5 ml of serum tends to depress these weights because of the anti-fsh present in the serum. Thirty millilitres of serum approximately doubles the seminal vesicle and prostate weights in intact males, whereas the testis weights are either unaffected or depressed. Based on the ventral prostate responses in Sprague-Dawley hypophysectomized males, the serum is estimated to contain about 25-μg equivalents of nih-lh-s8/ml. Both the serum of this mare and that of an untreated non-pregnant mare depressed the ovarian ascorbic acid level significantly, but the slopes of the responses to graded doses were flat and thus lh values could not be estimated by this procedure.

The biological activity of the serum from the mare treated with hcg as an antigen has been previously described. In earlier studies, Long-Evans hypophysectomized males, operated upon at 23 to 26 days, were used with treatment starting 15 days later. The testes were enlarged but the ventral prostate weights were unaffected by 16 ml of serum. In more recent findings, it has been found that if the animals are operated upon at 21 days and injections begun 4 days later significant ventral prostate weight responses can be obtained with 8 ml of serum. Attempts have been made to separate the gonadotrophic and anti-gonadotrophic activities in this serum by chemical fractionation. From the localization of activities in the γ-globulin fractions of the ammonium sulphate-ethanol procedure, and the α- and β-globulin fractions of the deae-cellulose procedure we conclude that the gonadotrophic and anti-gonadotrophic activities are not following any of the classical serum proteins for which these procedures were devised. It is suggested that most of the contaminating serum proteins could be eliminated by the sequential use of both procedures.