No abstract

Summary The distribution of inspired gas to each lung, time constants of the lungs and parameters of gas exchange were studied in 2 groups of horses (mean bwt 606 kg), anaesthetised using thiopentone and chloral hydrate and breathing room air. One group (n=4) had a downward curved abdominal contour (round‐bellied) and the other group (n=4) had an upward curved abdominal contour (flat‐bellied). An equal distribution of inspired gas between the lungs existed in both groups in dorsal recumbency. Flat‐bellied horses maintained this equal distribution in lateral recumbency whereas in round‐bellied horses an uneven distribution of tidal volume (VT) developed. The percentage of (VT) distributed to the dependent lung was 23% and 38% for left and right lateral recumbency respectively. The distribution of VT agreed with the ratio of time constants of the lungs in flat‐bellied horses but differed markedly from this ratio in round‐bellied horses suggesting that, in the latter, factors other than compliance and resistance play a role in distribution of ventilation. Round‐bellied horses had a lower PaO2 and a larger (A‐a)PaO2 than flat‐bellied horses in all body positions. The results are compatible with the known hypothesis that pressure exerted by abdominal contents on the dependent lung and diaphragm is an important factor in ventilation/perfusion mismatch of the anaesthetised horse.

Summary. Preovulatory bovine follices (n = 73) were collected at different times after the onset of oestrus until shortly before ovulation, which occurred at 24 \m=+-\1 \ m=. \ 4h after the peak concentration of LH in the peripheral blood. Non-atretic antral follicles (n = 9) of 15\p=n-\19mm were also collected from cows during the luteal phase of the oestrous cycle. Follicular fluid concentrations of dehydroepiandrosterone, androstenedione and oestrone, and of LH, FSH and prolactin were compared in 2-h periods relative to the LH plasma peak. Before the LH surge the concentrations of the steroids were much higher than in non-atretic luteal-phase follicles of similar size. From 0 to 6 h after the LH peak the steroid concentrations decreased sharply to remain low until ovulation; only that of androstenedione increased again after 14 h to remain constant. The ratio between the concentrations of androstenedione and dehydroepiandrosterone remained constant until 14 h after the LH peak; at 14 h it increased about 4-fold and remained high until ovulation. The ratio between the oestrone and androstenedione concentration increased gradually to a 10-fold higher value until at 14 h an abrupt decrease was observed. These changes indicate that after the LH peak androgen production is directly inhibited and, at a slower rate, the aromatizing activity. Androstenedione appeared to be the major aromatase substrate.Before the plasma LH peak the follicular fluid concentration of FSH was higher than in luteal-phase follicles; the concentrations of LH and prolactin were not different from those in luteal-phase follicles. About 4 h after the LH plasma peak the LH concentration in follicular fluid reached a maximum, which was one seventh of that in peripheral blood; it remained elevated until 20 h. The FSH concentration was higher after the LH plasma peak than before; just before ovulation it was still 2-fold higher. The concentration of prolactin fluctuated throughout the preovulatory development from the onset of oestrus until ovulation. It is suggested that oestradiol biosynthesis in bovine preovulatory follicles is terminated by an inhibitory action of the preovulatory LH peak on androgen production.

Specific receptor binding of estradiol (E-2) and dihydrotestosterone (DHT) was studied in human myometrial tissue and in human mammary cancer tissue. The inhibition of binding for E-2 and DHT by E-2, testosterone (T), DHT, dehydroepiandosterone (DHEA), dehydroepiandrosterone-sulfate (DHEA-S), androstendione (A) and 5-androstene-3beta, 17beta-diol (Adiol) was tested with the use of dextran-coated charcoal separation of bound and free E-2, respectively, and DHT. The percentage of binding inhibition was calculated with reference to the inhibition obtained with nafoxidine in a molar concentration ratio of 1,000 for E-2 binding, respectively, with cyproterone acetate in a molar concentration ratio of 10,000 for DHT binding. In 15 samples of myometrium tested, receptors were found for both E-2 and DHT. From 19 samples of mammary carcinoma tissue one showed no binding activity, three samples did bind E-2 only, five samples DHT only, and ten samples showed binding of both steroids. A 50% inhibition of E-2 binding, in myometrial as well as in tumor tissue, required a molar concentration ratio of 40 for Adiol, of more than 2,000 for DHEA. No significant inhibiting activity could be found for A up to a molar concentration ratio of 10,000 and for DHEA-S up to 40,000. With regard to DHT binding, Adiol is more active than E-2 and less active than T. Of the substances tested Adiol is therefore the only one which exerts a significant inhibiting influence at a molar ratio not far beyond the physiological range. This signifies that Adiol might interfere at the receptor level in the estrogenic stimulation of mammary cancer cells.

Urinary production rates of dehydroepiandrosterone (D) and dehydroepiandrosterone sulfate (DS) by isotope dilution, and the blood production rate of androstenedione (A) by continuous infusion technique have each been measured in 8 normal postmenopausal women. Both measurements were done in a group of 6 breast cancer patients. The cancer patients were at the time of the primary operation at least 6 yr postmenopausal; at the time of the study they were at least 3 yr after the operation. All of them were in good health and free of demonstrable recurrence of the tumor.The contribution of D and DS to urinary estrogens and the conversion of A to estrone were each determined in 8 normal postmenopausal women. Both measurements were done in the 6 breast cancer patients.The mean urinary production rate of D and DS were lower in the breast cancer patients than in the normal subjects. The difference was significant (p < 0.025) for DS. In the breast cancer patients the excretion of ll-deoxo-17-oxosteroids (11-DOKS) was lower than in the normal subjects. It is highly probable that the decreased production of D and DS is the cause of the low excretion of 11-DOKS in the patients.In 6 of the 14 experiments the specific activity of D isolated from the sulfate and the glucuronide fraction was not consistent with the model of van de Wiele et al. It is likely that in these cases neither D-glucuronide nor D-sulfate could be considered a unique specific metabolite of the D-and the DS-pool respectively. The contribution of D and DS to urinary estrogens was low (less than 0.01%) in both normals and in breast cancer patients.In the normal subjects we found a mean metabolic clearance rate of A of 1843 ± 131 (SE) liter per day and a mean plasma-level of A of 0.83 ± 0.13 ng per liter leading to a daily blood production rate of 1.64 ± 0.38 mg of A. In the breast cancer patients we found a mean metabolic clearance rate of 2398 ± 4 2 5 (SE) liter per day and a mean plasma-level of A of 0.60 ± 0.12 \xg per liter leading to a daily blood production rate of 1.46 ± 0.39 (SE) mg of A.The conversion of circulating androstenedione to estrone was 2.5 ± 0.3 ( S E ) % in the normal subjects and 2.9 ± 0.2 ( S E ) % in the breast cancer patients. Both in the normal subjects and in the breast cancer patients a daily estrone production of approximately 40 M*g can therefore be accounted for by the conversion of plasma born androstenedione. (/ Clin Endocrinol Metab 37: 101, 1973)