Direct effects of a luteinizing hormone-releasing hormone agonist on intratesticular levels of testosterone and interstitial fluid formation in intact male rats.
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Animals↗
Biomedical subjects
I Cooper
Publications and source records attributed to I Cooper.
Testicular interstitial fluid as a monitor for changes in the intratesticular environment in the rat.
The use of testicular interstitial fluid (IF) collected from the rat testis has been validated as (1) an index of the total extracellular extratubular fluid volume of the testis (which reflects the permeability of testicular capillaries) and (2) as a means of measuring changes in the interstitial hormonal environment. The former was tested by comparing the albumin 'space' with the volume of recovered IF in the same testes from control and bilaterally cryptorchid rats sampled at 0-40 h after injection of hCG. Although the volume of IF recovered was on average only 50% of the albumin 'space', both measures increased in parallel after hCG injection and were always closely correlated (P less than 0.001) over a 4- to 5-fold range. The volume of recovered IF increased with age in parallel with increase in testicular weight, and the testosterone concentration in IF paralleled changes in peripheral serum, increasing from 45 to 80 days of age and then declining. After injection of 25 micrograms bovine LH, testosterone levels in IF, spermatic venous (SV) and peripheral venous (PV) blood increased up to 10-fold by 1 h and returned to control levels over the next 11 h. Testosterone levels in IF were always considerably higher than those in SV blood, but this difference was not constant. Subcutaneous injection of rats with an LH-RH agonist resulted in parallel increases in the serum levels of LH and in the IF and PV levels of testosterone. However, at 6 h there was an 'LH-independent' secondary increase in testosterone levels which was associated with an increase in IF volume, reflecting an increase in capillary wall permeability and hence increased transport of LH into the testis.
Age Factors↗
Stimulation of Leydig cell testosterone secretion in vitro and in vivo in hypophysectomized rats by an agonist of luteinizing hormone releasing hormone.
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Animals↗
Stimulatory effect of LHRH and its agonists on Leydig cell steroidogenesis in vitro.
Short-term (4 h) incubation of collagenase-dispersed Leydig cells from adult rats in the presence of an LHRH agonist caused a 2-3-fold stimulation (P less than 0.001) of testosterone production. This effect was dose-dependent and as little as 5 x 10(-11) M LHRH agonist caused significant stimulation whilst maximal effects were achieved with 10(-9) M concentrations. Stimulation of steroidogenesis by LHRH agonist was prevented by addition of an antiserum specific for the peptide, but was exaggerated in the presence of the phosphodiesterase inhibitor MIX, suggesting the involvement of cyclic AMP in the response of the Leydig cells to the agonist. Native LHRH caused a similar degree of stimulation of testosterone secretion to LHRH agonist but concentrations 1000 times greater than those of the agonist were required to achieve this, a finding consistent with the known affinities of these 2 peptides for the Leydig cell LHRH-receptor. The addition of LHRH agonist also enhanced (P less than 0.001) testosterone secretion by adult rat Leydig cells in response to hCG or dibutyryl cyclic AMP, and this effect was still evident in the presence of maximally-stimulating concentrations of these factors. LHRH agonist also stimulated testosterone secretion by Leydig cells from immature rats, but this effect differed from that in the adult in being of smaller magnitude and being restricted to effects on basal secretion or secretion elicited by low concentrations of hCG. These results show for the first time (a) that LHRH and its agonists can exert effects on Leydig cell steroidogenesis during short-term incubation, and (b) that these effects are stimulatory, which contrasts with the inhibitory effects reported after long-term (2-3 days) exposure of Leydig cells to LHRH agonists in vivo and in vitro. The availability of this simple and rapid measure of a biological action of LHRH on the Leydig cell should enable its precise mode of action to be determined, and should throw light on the physiological role of endogenously produced testicular 'LHRH'.
1-Methyl-3-isobutylxanthine↗
The mode of action of LHRH agonists on the rat Leydig cell.
The relationship between LHRH agonist-receptor interaction and subsequent stimulation of steroidogenesis has been investigated using dispersed adult rat Leydig cells. Binding of 125I-labelled LHRH agonist to these cells was rapid and was readily and completely reversible, which contrasted with the binding of 125I-labelled hCG which was never completely reversible and which became progressively less reversible with increase in time. Following 125I-LHRH agonist-receptor interaction for 5 min at 21 degrees C, over 80% of the bound hormone dissociated at a fast rate (t 1/2 1.5 min) and the remainder at a slower rate (t 1/2 20 min). Following LHRH agonist-receptor interaction for a longer period (45 min) at 21 degrees C, only the slower of these 2 components of dissociation was evident, although binding was still completely reversible. Evidence was also obtained that following preincubation of Leydig cells for 2 hr at 34 degrees C with a near-saturating concentration (2000 pg/ml) of unlabelled LHRH agonist, all or most of the bound hormone dissociated during subsequent incubation at 21 degrees C. Incubation of Leydig cells at 34 degrees C in the continuous presence of either a low dose (1 pM) of hCG or a high dose (2000 pg/ml) of LHRH agonist resulted in similar percentage stimulation of testosterone secretion with a similar time lag (2 h) before this increase was evident. Preincubation with this dose of hCG for as little as 15 or 30 min still led to increased testosterone secretion following removal of the free hormone. In contrast, preincubation with LHRH agonist for up to 2 h was without subsequent stimulatory effect, presumably due to dissociation of the bound hormone from its receptors. Therefore, for LHRH agonist to stimulate Leydig cell steroidogenesis in vitro, it must be present continuously in the incubation medium, and the implications of this with respect to the secretion and mode of action of 'testicular LHRH' in vivo are discussed.
Animals↗
The secretion, measurement, and function of a testicular LHRH-like factor.
In this paper we have demonstrated the presence and secretion within the testis of a factor that is immunologically distinct from LHRH, but that has receptor-binding and bioactive features similar to LHRH. The major source of this LHRH-like factor is probably the Sertoli cell and, as its site of action appears to be restricted to the Leydig cells, it is possible that it is one of the means by which the Sertoli cell has been postulated to regulate the Leydig cell. All of the available evidence suggests that the action of the LHRH-like factor on the Leydig cell is inhibitory, and it may mediate some or all of the negative effects on the Leydig cell of LH and hCG. The precise role of the LHRH-like factor, particularly under physiological conditions (i.e., low level stimulation with LH), remains to be determined, but the availability of methods for its extraction, measurement, and inactivation should enable this problem to be resolved within the near future. Moreover, the recognition that Leydig cell function may be regulated by local factors within the testis should open up new avenues of research that may lead to improved methods for the regulation of fertility in the male.
Aging↗
Inter-generational transmission of incest.
The majority of reported incest cases involve sexual relations between one generation and another, the most common being father-daughter incest. The increased availability of clinical data on incest has revealed an aspect of the problem that has received little attention in clinical literature. Incest can involve three generations in a family rather than two. It is possible for incest to be "transmitted" from one generation to the next through several patterns. In some cases, the mother in a family of father-daughter incest has herself been a victim of incest with her own father. With a history of unresolved incest with their own fathers, these women are unable to prevent an incest relationship between their husbands and daughters. Another pattern involves situations where the father in the father-daughter incest relationship has been the victim of father-son incest in his youth. The psychodynamics of these patterns of intergenerational transmission of incest are described, with clinical examples from the authors' work, as well as from the literature.
Adolescent↗
Variation in the steroidogenic responsiveness of isolated rat Leydig cells.
Isolated Leydig cells were prepared from adult rat testes by (1) mechanical dissection, (2) collagenase dispersion or (3) mechanical dissection followed by collagenase dispersion, and their functional characteristics were assessed. Compared with Methods 2 and 3, mechanical isolation alone resulted in the purest preparation of Leydig cells but the lowest yield. Leydig cells isolated by any of the 3 methods had similar numbers of LH- and LH-RH receptors, but cells isolated by Methods 1 and 3 showed poor testosterone responsiveness compared to cells isolated by Method 2. This reduced response was evident following stimulation with hCG, dibutyryl cyclic AMP or an LH-RH agonist, and could not be accounted for simply on the grounds of diminished cell viability. It is concluded that Leydig cells in the rat testis are particularly sensitive to mechanical intrusion, and this is an important factor to bear in mind when preparing Leydig cells or when comparing results between laboratories.
Animals↗
Sertoli-Leydig cell communication via an LHRH-like factor.
The primary function of the testosterone secreted by Leydig cells is the maintenance of spermatogenesis and hence fertility. This action of testosterone is mediated by the Sertoli cells which nourish and support the developing spermatozoa. As normal Sertoli cell function is so critically dependent on normal Leydig cell function, a regulatory influence of the Sertoli cells on the Leydig cells has been suggested. Indeed, follicle-stimulating hormone (FSH), which acts only on Sertoli cells, can also cause profound changes in Leydig cell function, although how this is effected is unknown. We recently hypothesized that the Sertoli cell might be the source of a luteinizing hormone releasing hormone (LHRH)-like factor which we detected in the interstitial fluid surrounding the Leydig cells. As injected LHRH agonists cause impairment of gonadal function and directly inhibit FSH-induced changes in Leydig cell function through specific membrane receptors, this 'LHRH-like' factor has all the correct credentials for the postulated messenger between the Sertoli and Leydig cells. Here, we strengthen this case by demonstrating that seminiferous tubules from both the rat and the stumptailed macaque (Macaca arctoides) contain a factor which has LHRH-like receptor-binding and biological activity in vitro, but which is immunologically distinct from native LHRH. We have also shown that this factor is secreted in vitro by cultured rat Sertoli cells.
Animals↗
Reduced prostaglandin levels in the semen of men with very high sperm concentrations.
The prostaglandin levels have been measured in a group of men with sperm concentrations greater than 300 X 10(6)/ml and compared with the levels in men with sperm concentrations of 50 to 150 X 10(6)/ml. The distribution of the PG levels in all groups was highly skewed but the data could be transformed to a normal distribution by taking logarithms. Comparison of the PG levels showed a highly significant lowering of the PG levels in the polyzoospermic group when compared wieth either of the groups with normal sperm concentrations.
Cell Count↗
Prostaglandin concentrations in the semen of fertile men.
The PG concentrations in the semen of 23 fertile men were 73 microgram PGE/ml, 267 microgram 19-OH PGE/ml, 2.1 microgram PGF/ml and 18.3 microgram 19-OH PGF/ml. The wide ranges of concentrations found for the PGEs (2-272 microgram/ml) and for the 19-OH PGEs (53-1094 microgram/ml) throw some doubt on the previously established correlation between infertility and low prostaglandin concentrations.
Adult↗
Hodgkin's disease.
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Antineoplastic Agents↗
The measurement of E and 19-hydroxy E prostaglandins in human seminal plasma.
A method is described which measures the four main prostaglandins of human semen (PGE1, E2, 19-hydroxy PGE1, and 19-hydroxy PGE2). For routine measurements E1 and E2 are measured together as are 19-OH E1 and 19-OH E2. These are measured by forming oximes in aqueous solution extraction, methylation and trimethyl silylation followed by gas chromatography. The method has sufficient sensitivity to measure the levels found in the majority of semen samples. The normal range in men with proven fertility was 90 to 260 mug/ml of 19-hydroxy Es and 30-200 mug/ml of Es.
Adult↗
Potassium supplementation during diuretic therapy.
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Administration, Oral↗
Group sessions for new mothers.
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Child Health Services↗
Health care for Rockaway children.
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Child Health Services↗
Energy metabolism in human platelets: interrelationship between glycolysis and oxidative metabolism.
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Albumins↗
Correlation of immunological surface antigens with survival in diffuse large cell lymphoma.
The prognostic value of immunophenotyping lymphomas with a panel of monoclonal antibodies (Mab) to various lymphoid antigens was assessed by studying 47 cases of diffuse large cell lymphoma. Cell suspensions were analysed by flow cytometry after labelling by indirect immunofluorescence. Thirty-eight cases were demonstrated to be of B cell and nine of T cell phenotype. Univariate analysis demonstrated that survival was significantly longer in patients expressing higher levels of HLA-DR (p = 0.01) and normal levels of CD8 (p = 0.04) but was not significantly associated with any of the other antigens. Our results support the possible value of HLA-DR in determining the prognosis of patients with diffuse large cell lymphoma.
Adult↗