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MARIAM KRISHNAMURTI and E. T. BELL

Summary.

The specificity of the assay method for the gonadotrophin inhibiting factor (gif) has been studied in two ways. In the first part of the study the biological activity of various gonadotrophin preparations remaining after heating at 100°C for 1 hr was measured. In the second part the effect of these hormones on the bio-assay method for the gif was investigated.

Following heating it has been shown that most, but not all, of the biological activity of the preparations studied is destroyed when assayed by specific methods. Gonadotrophins derived from ovine pituitary tissue, but not from human urine, have been demonstrated to be capable of causing a uterine response in the assay for the gif.

It is concluded that the assay method for the gif is not specific. For this reason care must be taken in interpreting the results of assays of the gif in clinical situations in which high endogenous gonadotrophin levels are likely to be present.

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E. T. BELL and S. F. LUNN

Summary.

The effect of the administration of 50 i.u. pregnant mare's serum gonadotrophin (pmsg) alone or the same dosage of this hormone followed 72 hr later by 25 i.u. human chorionic gonadotrophin (hcg) on ovarian wet and dry weight has been investigated in three colonies of rats of the Wistar strain.

Alterations in the ratio of the wet to dry ovarian weight were noted following treatment of pmsg; these were less marked after hcg administration.

The maximum ovarian weight obtained following hormonal treatment varied between the three colonies of rats but the pattern of response was similar. The results did not appear to be influenced by the body weight of the animals.

It is suggested that differences in ovarian weight between the three rat colonies may influence the results obtained in the ovarian ascorbic acid depletion (oaad) and ovarian cholesterol depletion (ocd) tests.

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E. T. BELL, M. F. PARKES and D. W. CHRISTIE

Summary.

Results of urinary assays of total gonadotrophic activity, fsh and lh in ovariectomized Beagle bitches are reported. Urine samples collected from animals in metabolism crates were extracted by the tannic acid precipitation technique.

Very low levels of total gonadotrophic activity were found when the mouse uterus test was employed; activity being undetectable in six out of thirteen animals. Levels of fsh could generally be measured by the mouse ovarian augmentation test. In a group of six bitches, the individual means for fsh output ranged from <4·5 to 21·6 i.u./24 hr. Levels of lh were assayed by the ovarian ascorbic acid depletion test in a series of ten animals and values ranged from <5·0 to 10·4 i.u./24 hr.

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G. L. FOSS, E. T. BELL, F. J. W. LEWIS, J. A. LORAINE and B. R. POLLARD

Summary.

The effect of clomiphene on the sperm count and hormone excretion is described in a patient with Klinefelter's syndrome, having a 47 XXY karyotype, and in whom a testicular biopsy showed small areas of spermatogenesis.

Clomiphene stimulated the production of morphologically normal motile spermatozoa in the absence of any marked effect on hormone output.

Possible explanations for these findings are discussed.

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GWYNETH E. JONES, A. R. BOYNS, E. H. D. CAMERON, E. T. BELL, D. W. CHRISTIE and M. F. PARKES

Recent reports have recorded results of the simultaneous measurement of the concentration of progesterone and LH in the blood plasma of the dog during the oestrous cycle and pregnancy (Jones, Boyns, Bell, Christie & Parkes, 1973) and of oestradiol-17β, progesterone and LH during the oestrous cycle (Jones, Boyns, Cameron, Bell, Christie & Parkes, 1973). We report here the results of simultaneous measurement of oestradiol-17β, progesterone and LH in the plasma of the Beagle bitch during pregnancy.

Four Beagle bitches were maintained under controlled conditions and blood samples were collected between 14.00 and 15.00 hours; all animals were parous. The onsets of pro-oestrus and oestrus were determined by methods previously described (Christie & Bell, 1971). The bitches were each mated on two

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S P Sébert, M A Hyatt, L L Y Chan, M Yiallourides, H P Fainberg, N Patel, D Sharkey, T Stephenson, S M Rhind, R C Bell, H Budge, D S Gardner and M E Symonds

The recent discovery of an association between body composition, energy intake and the fat mass and obesity-associated (FTO) gene represents a promising new therapeutic target in obesity prevention. In a well, pre-established large animal model, we investigated the regulation of FTO gene expression under conditions either leading to obesity or increased risk of obesity related disorders: i) a sedentary ‘Western’ lifestyle and ii) prenatal exposure to nutrient restriction. Pregnant sheep were either fed to fully meet their nutritional requirements throughout gestation or 50% of this amount from early-to-mid gestation. Following weaning, offspring were either made obese through exposure to a sedentary obesogenic environment or remained lean. A significant positive relationship between placental FTO gene expression and fetal weight was found at 110 days gestation. In both the newborn and adult offspring, the hypothalamus was the major site of FTO gene expression. Hypothalamic FTO gene expression was upregulated by obesity and was further increased by prenatal nutrient restriction. Importantly, we found a strong negative relationship between the hypothalamic FTO gene expression and food intake in lean animals only that may imply FTO as a novel controller of energy intake. In contrast, FTO gene expression in the heart was downregulated in obese offspring born to nutrient restricted mothers. In addition, FTO gene expression was unaffected by obesity or prenatal diet in insulin-dependent tissues, where it changed with age possibly reflecting adaptations in cellular energetic activity. These findings extend information gained from human epidemiology and provide new insights into the regulation of in vivo energy metabolism to prevent obesity.