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B P Setchell

Publications and source records attributed to B P Setchell.

At least 109 records · Page 6Linked to original sources

Effects of passive immunization against testosterone on serum and pituitary gonadotrophins: implications for the relative importance of androgens and inhibin in the control of gonadotrophin secretion in the male rat.

The acute effects of a specific reduction in androgen feedback to the hypothalamus and pituitary gland have been investigated in male rats by passive immunization against testosterone. An ovine antiserum raised against testosterone which had been conjugated through position 3 to bovine serum albumin was employed. Negative feedback control by androgens was effectively reduced by administration of the antiserum, as shown by an increase in levels of LH in the circulation. Immunized animals had a high concentration of testosterone in the circulation of which virtually all was tightly bound to antibody. In normal animals specific increases of serum LH concentration were obtained at all ages using a low dose of antiserum. At higher doses, serum FSH concentration was also increased. The LH response was reduced by anaesthesia and sham-operation. In sham-operated rats given a high dose of antiserum for 3 days the serum concentrations of LH and FSH could not be distinguished from those which followed castration while differences were found in the pituitary contents. It was concluded that testicular androgen provides an important inhibitory feedback control of secretion of FSH as well as that of LH in the adult male rat. Some of the data can best be explained by the action of inhibin as a minor or alternative inhibitor of FSH secretion.

Aging↗

Responsiveness of the pituitary gland to androgens and of the tests to gonadotrophins following damage to spermatogenesis in rats.

To test the interaction of androgen and inhibit feedback on the pituitary gland, inhibin-type feedback from the testes was reduced when they were made aspermatogenetic by bilateral ligation of the efferent ducts or local heating (43 degrees C for 30 min). There were only minor effects on the subsequent response of the pituitary gland to the removal of androgen feedback by the administration of antiserum against testosterone or by castration. However, in the antiserum-injected animals the steroidogenic response of the testis to the increased serum concentrations of LH was less in aspermatogenic than in control rats. Furthermore, unilateral aspermatogenesis was associated with reduced testosterone output by the treated testis and with compensatory increased output by the contralateral control testis, despite the absence of significant changes in serum LH and normal peripheral levels of testosterone. This suggests that the tubules can regulate the responsiveness of the Leydig cells to LH.

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Inhibin.

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Measurement of the motility of rat spermatozoa collected by micropuncture from the testis and from different regions along the epididymis.

Spermatozoa from the testis and various regions along the epididymis of the rat were collected by micropuncture and their motility after dilution was estimated over a 15-min period by using a Quantimet image analyser. The motility of sermatozoa from the rete testis and seminiferous tubules was too low to be measured. The estimate of motility of spermatozoa from the proximal caput epididymidis was much lower than that of spermatozoa from the other regions. Spermatozoa from the distal part of the caput showed sustained motility for 15 min, whereas those from the caudal region and ductus deferens, although active initially, became less active during this period.

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The concentration of carnitine in the luminal fluid of the testis and epididymis of the rat and some other mammals.

Luminal fluid was collected by micropuncture techniques from the testis and epididymis of the rat, hamster, rabbit, boar and ram and the concentration of free L-carnitine in the fluid was estimated using enzymic methods. Carnitine was present in the testicular fluid of the rat in concentrations less than 1 mM but increased down the epididymis to reach 53 mM in luminal fluid from the cauda epididymidis, approximately 2000 times higher than in blood plasma. A high concentration was first found in the luminal fluid from the distal caput epididymidis, at about the point where the spermatozoa become motile. Carnitine was also present in the epididymal luminal fluid of the other species studied; the amounts were not as high as those in the rat but were still higher than those in blood plasma.

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Lipid changes in boar spermatozoa during epididymal maturation with some observations on the flow and composition of boar rete testis fluid.

The flow rate and composition of boar rete testis fluid were similar to those in other species studied previously. The total phospholipid phosphorus and phospholipid fatty acid content of boar spermatozoa decreased during maturation in the epididymis but the level of phospholipid phosphorus was slightly higher in ejaculated spermatozoa than in epididymal spermatozoa. During passage of the spermatozoa from the testis to the cauda epididymidis, loss of the major saturated acids (palmitic, 16:0, and stearic, 18:0) was extensive but partly recovered in the ejaculated spermatozoa. The mass of docosapentaenoic (22:5) and docosahexaenoic (22:6) acids tended to decrease continuously during maturation but the percentage of 22:6 by weight of total phospholipid fatty acid reached a maximum in the epididymis. Ejaculated boar spermatozoa contained considerably more phospholipid and phospholipid fatty acid than did ejaculated bull or ram spermatozoa.

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Lipid changes during epididymal maturation in ram spermatozoa collected at different times of the year.

The phospholipid and phospholipid fatty acid content of ram spermatozoa decreased during maturation in the epididymis but interpretation of the results was complicated by a possible seasonal factor. Loss of individual fatty acids was selective, resulting in an increase in unsaturation during maturation. Testicular spermatozoa and fluid collected directly into chloroform-methanol contained about 7 times more neutral lipid fatty acid than testicular spermatozoa collected for 6--18 h, separated from the rete testis fluid and then extracted; the difference was not due to lipid in the rete testis fluid. Thin-layer chromatography indicated that cholesterol esters and triglycerides were the neutral lipids which were not lost during collection. Epididymal spermatozoa contained only slightly less neutral lipid fatty acid than continuously collected testicular spermatozoa.

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The effects of long-term administration of either a crude inhibin preparation or an antiserum to FSH on serum hormone levels, testicular function and fertility of adult male rats.

Adult male rats were given either daily injections of ram rete testis fluid for periods of up to 70 days or injections of an antiserum against FSH every 3 days for 90 days. Compared with the control groups, the rats injected with ram rete testis fluid had lowered serum FSH levels, but only at treatment periods of 30 days and less. The levels of LH and testosterone in serum, testicular fluid secretion, sperm counts, testis weights and fertility were not affected by rete testis fluid treatment. The rats injected with anti-FSH serum exhibited an impairment of fertility which was never complete and evident only after 49 days of treatment. After 90 days of anti-FSH treatment, testis weight and free serum FSH were reduced, but sperm counts, testicular fluid secretion and serum levels of LH and testosterone were not affected.

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The evidence that inhibin must exist.

The historical development of the 'inhibin' hypothesis is restated and the recent evidence reviewed. The circumstantial evidence for inhibin now seems very strong, and it probably acts in both sexes. Active materials have been isolated from several sources but it is not clear which is the circulating form of inhibin and a reciprocal relationship between circulating inhibin and FSH levels has not yet been demonstrated. Nevertheless, it appears that we may be optimistic about the existence of inhibin though the importance of its role as a physiological feedback inhibitor is still controversial.

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The effect of rete testis fluid on the metabolism of testicular spermatozoa.

The O2 uptake of spermatozoa collected from the rete testis of conscious rams and boars has been measured polarographically either in the rete testis fluid (RTF) in which they were collected or in a synthetic saline medium (S-RTF) made to resemble the ionic composition of RTF as closely as possible. In both species, O2 uptake of the testicular spermatozoa was higher in RTF than in S-RTF. The addition of some of the organic constituents of RTF was without effect on O2 uptake. Pyruvate, lactate, acetate or alanine increased the O2 consumption of ram spermatozoa in S-RTF. Lactate had no effect on but acetate increased the O2 consumption of pig testicular spermatozoa. Phospholipid phosphorus and fatty acids decreased during incubation of ram spermatozoa in RTF and S-RTF. The addition of substances which increased the O2 consumption of the spermatozoa in S-RTF was without effect on the lipid composition. The fatty acid composition of the phospholipids and the proportions of the various phospholipids were unaffected by incubation. These results indicate that rete testis fluid has an appreciable effect on the metabolism of the spermatozoa it contains, and that this effect cannot be mimicked by any of the known organic constituents of the fluid.

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Association of exogenous phospholipids with spermatozoa.

Boar, bull and ram spermatozoa were studied after incubation in a medium containing phospholipids. Autoradiography and birefringent examination of spermatozoa after incubation with labelled phosphatidylcholine indicated that liposomes of this phospholipid associated with spermatozoa. The association was almost instantaneous. The large multilayer liposomes formed during the experimental procedure resulted in a few of the spermatozoa acquiring most of the phosphatidylcholine. Little phosphatidylcholine was observed unassociated with spermatozoa although measurements of the partition between spermatozoa and medium showed that only boar spermatozoa associated with almost all the phospholipid. No evidence was obtained that phosphatidylethanolamine or phosphatidylinositol associated with the spermatozoa.

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Feedback control by the testis of gonadotrophin secretion: an examination of the inhibin hypothesis.

Spermatogenesis in rats was interrupted by local X-irradiation, heat or ligation of the testicular efferent ducts. A significant and specific rise in the serum level of FSH occurred 5--8 days after ligation of the efferent ducts, reaching twice the value observed in sham-operated controls by 21 days after the operation. After the testes were heated to 43 degrees C for 30 min, the serum levels of both LH and FSH were raised within 3 days and remained so up to 50 days after treatment. After X-irradiation, no changes in the concentration of FSH were observed in the first 21 days after treatment, but the serum levels of both gonadotrophins were increased at 49 days. By comparing the relative increases in the concentrations of FSH and LH after germ cell damage with those occurring after castration, it was evident that testicular androgens could account for only part of the normal feedback control of FSH secretion; at least one third of the inhibition of FSH secretion appeared to be due to non-androgenic sources, presumably 'inhibin'.

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