SEARCH · PubMed Health

Results for “testosterone”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,027 records · Page 57Linked to original sources

PubMed1999

Different mechanisms for testosterone-induced relaxation of aorta between normotensive and spontaneously hypertensive rats.

The tension in isolated ring preparations of the thoracic aortae from Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) was measured isometrically to study the differences in testosterone-induced relaxation between WKY and SHR aortic rings. Testosterone (9 to 300 micromol/L) induced a concentration-dependent relaxation in both WKY and SHR aortic rings, and the relaxation induced by testosterone was greater in SHR than WKY. The relaxation induced by testosterone was significantly reduced by denudation of endothelium in SHR but not WKY. Indomethacin, an inhibitor of cyclooxygenase, and N(G)-nitro-L-arginine, an inhibitor of nitric oxide (NO) synthase, showed little influence on the relaxation induced by testosterone in both WKY and SHR aortic rings. Glibenclamide, a selective inhibitor of ATP-sensitive potassium channels, significantly reduced the relaxation induced by testosterone in both WKY and SHR aortic rings, although the extent of reduction was greater in WKY than SHR. On the other hand, 4-aminopyridine, a selective inhibitor of voltage-dependent potassium channels, and tetraethylammonium, an inhibitor of calcium-activated potassium channels, significantly reduced the relaxation induced by testosterone in SHR but not WKY. These results suggest that the mechanisms of testosterone-induced vasorelaxation in both WKY and SHR involve, in part, ATP-sensitive potassium channels in the thoracic aortae and that in SHR aortic rings, testosterone may release endothelium-derived substances that may cause hyperpolarization of the cells by a mechanism that involves potassium channels. Moreover, the data show differences between WKY and SHR in the function of ATP-sensitive, voltage-dependent, and calcium-activated potassium channels.

4-Aminopyridine↗

PubMed1994

Effects of testosterone on hypoxic ventilatory and carotid body neural responsiveness.

Hypoxic (HVR) and hypercapnic ventilatory responses (HCVR) are known to be influenced by the administration of testosterone, but whether the hormone acts centrally or peripherally is unknown. To determine whether testosterone alters HVR, HCVR, and carotid sinus nerve (CSN) responsiveness to hypoxia, we compared the ventilatory and CSN responses of neutered male cats treated with testosterone with those of placebo-treated cats. Testosterone treatment increased resting ventilation and CO2 production but did not change end-tidal or arterial PCO2, implying that alveolar ventilation per unit CO2 production was unaltered. Testosterone treatment raised the HVR shape parameter A value 63% in the awake animals (from 16.9 +/- 4.2 to 28 +/- 4, p < 0.05) and 69% in the anesthetized cats (from 22.4 +/- 0.9 to 37.8 +/- 3.7, p < 0.05). Testosterone also augmented the HCVR slope S in awake cats (from 0.17 +/- 0.02 to 0.25 +/- 0.04, p < 0.05). Placebo treatment did not change HVR or HCVR. The CSN response to hypoxia was greater in the testosterone-treated than in the placebo-treated animals (A = 53.6 +/- 7.1 versus 27.1 +/- 5.5 respectively, p < 0.05). The crossplot of the simultaneously measured CSN activity and ventilation during progressive hypoxia showed that the central nervous system translation of CSN output into ventilation was similar in the hormone- and placebo-treated groups. Unilateral, proximal sectioning of the CSN decreased the ventilatory and the CSN responses to hypoxia in the testosterone-treated animals but not in the placebo group. These results indicated that testosterone increased hypoxic and hypercapnic ventilatory responsiveness and increased hypoxic sensitivity of the carotid body.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1970

Studies on testosterone metabolism in subjects with testicular feminization syndrome.

The metabolism of radioactive testosterone simultaneously administered intravenously and either orally or percutaneously has been studied in seven patients with the syndrome of testicular feminization and compared with that of normal males and females. This investigation was carried out in order to determine the relative contribution to urinary 17-oxo and 17beta-hydroxy androstane steroids of labeled testosterone, according to its mode of administration. In normal males the yields of urinary 5alpha-androstane-3alpha,17beta-diol (androstanediol) originating from either an intravenous or a percutaneous dose of testosterone were respectively 3 and 6 times higher than those arising from an oral dose which perfuses the liver directly. These data indicate that in normal males, testosterone might be 5alpha-hydrogenated outside the liver. By contrast in patient with feminizing testes, because the contribution to androstanediol of radioactive testosterone is identical whatever its mode of administration, the extrahepatic 5alpha-reduction of this substrate seems very unlikely. The metabolic abnormalities observed in patients with testicular feminization syndrome may be reproduced in normal males by estrogen treatment. Nevertheless, the sensitivity of the patients to estrogen seems to be 10 times greater than that of normal males. This sensitivity was appreciated from the reduction of radioactive testosterone intravenously injected to urinary 17beta-hydroxy-5alpha-androstan-3-one and androstanediol and also from the level of plasma binding for testosterone. This level was significantly higher (P < 0.05) in patients with feminizing testes than in normal males. The level increased dramatically after administration of a low dose of estrogen whereas this effect was not observed in normal males under the same experimental conditions. In light of these results the defect of extrahepatic 5alpha-reduction of testosterone observed in patients with feminizing testes does not necessarily reflect an enzymatic impairment but might be related to an abnormal synthesis of plasma binding protein(s) under the effect of circulating estrogens so that an abnormally small amount of unbound testosterone may be available in target cells for 5alpha-reduction.

Adult↗

PubMed1996

Relative potency of testosterone and dihydrotestosterone in preventing atrophy and apoptosis in the prostate of the castrated rat.

Although dihydrotestosterone (DHT) is the principal androgen in the prostate, testosterone can also act as an androgen in this tissue. To determine the relative potencies of testosterone and DHT in preventing prostate regression, castrated rats were implanted for 4 d with varying doses of testosterone in the presence or absence of the 5alpha-reductase inhibitor finasteride. In the absence of finasteride, testosterone in the prostate is converted to DHT, creating an intraprostatic DHT dose response. In the presence of finasteride, this conversion is blocked, and an intraprostatic testosterone dose response is achieved. DHT was 2.4 times more potent than testosterone at maintaining normal prostate weight and duct lumen mass, a measure of epithelial cell function. The two androgens were equipotent at preventing DNA fragementation and expression of testosterone-repressed prostate message, two measures of apoptosis (cell death). The intraprostatic testosterone concentration that results from finasteride treatment in rats is sufficient to inhibit apoptosis but will not maintain normal epithelial cell activity. In conclusion, whereas DHT is more potent than testosterone at stimulating prostate epithelial cell function as measured by ductal mass, the two androgens are equipotent at preventing prostate cell death after castration. These results explain why finasteride causes prostate involution in the rat with minimal evidence of prostate cell death.

Animals↗

PubMed1998

Age-associated testosterone decline in men: clinical issues for psychiatry.

OBJECTIVE: The author summarizes current knowledge about the diagnosis and treatment of testosterone decline in healthy aging men and the associated clinical issues for psychiatry. METHOD: A MEDLINE search was conducted in which the search terms "male climacteric," "male menopause," "andropause," "viropause," "low-testosterone syndrome," and "testosterone replacement therapy" were used. Literature published before 1966 was identified by reviewing the reference lists of later publications. RESULTS: Manifestations of testosterone deficiency have included depression, anxiety, irritability, insomnia, weakness, diminished libido, impotence, poor memory, reduced muscle and bone mass, and diminished sexual body hair. Although testosterone levels decline with age, there is great interindividual variability, and the connection between serum testosterone levels and clinical psychiatric signs and symptoms is not clear-cut, since other hormonal changes are implicated as well. Testosterone replacement therapy may offer hypogonadal men benefit, but long-term studies on its efficacy and safety are lacking. Comprehensive biopsychosocial assessment should be a routine part of the evaluation of complaints of low-testosterone syndrome in men. CONCLUSIONS: Testosterone decline/deficiency is not a state strictly analogous to female menopause and may exhibit considerable overlap with primary and other secondary psychiatric disorders.

Aged↗

PubMed1981

Influence of antisera, purification procedures, and tracers on validity of a testosterone radioimmunoassay.

The levels of testosterone in pooled plasma from men and from women were measured by radioimmunoassay. Testosterone was isolated from plasma either by ether extraction (direct procedure) or by chromatography of the ether extract (chromatographic procedure). Three different antisera (all raised against testosterone-3-oxime albumin) were employed. An additional variable was the use of two tracers, [3H] testosterone and [125I] histamine testosterone. The latter tracer was employed in both a freshly prepared form and two months after labelling. The old tracer was used both in a nonpurified and repurified form. The results were compared with those given by one of the antisera using the assay with chromatography. The validity of this assay was verified earlier using a test of radiochemical purity. In the statistical evaluation of the data, it was found that the assays of both plasma pools gave the same results as the validated assay, even with two other antisera, but only when the chromatographic purification was used. The direct assays gave significantly increased values for testosterone in the male plasma pool with one antiserum, and in the female plasma pool with all three antisera. It is concluded that those assays maybe considered valid which give results statistically indistinguishable from those obtained by the valid assay. These were all chromatographic assays and, in the man, also two direct assays. The comparison of [3H] testosterone and [125I] histamine testosterone as tracers did not indicate any major differences in the validity of the assays. When the 125I-tracer was employed, a moderate (1.5-2 fold) increase of sensitivity was seen with all three antisera, and the antisera could be used in a 10-40 times higher dilution. Furthermore, it was possible to use [125I] histamine testosterone and obtain practically the same results after two months, whether repurified or not.

Adult↗

PubMed1985

Plasma free testosterone--is an index sufficient?

Only about 50% of women who are clinically hirsute have a raised total plasma testosterone concentration; in those cases where the total testosterone is normal the free testosterone may, in fact, be raised. Since the measurement of free testosterone is tedious, workers have used an androgen index or a calculated free testosterone concentration from the measurements of total testosterone and sex-hormone-binding globulin. We have examined the correlation between measured free testosterone, a derived free testosterone and an androgen index in hirsute women, normally menstruating women and non-hirsute women on oral contraceptive therapy. These three measures of the free testosterone concentration in blood gave similar results in all cases.

Adolescent↗

PubMed2000

Modeling of circadian testosterone in healthy men and hypogonadal men.

The testosterone circadian rhythm has been reported extensively in the literature and has been described by a cosine function. Typically, these data are measured at frequent and regular (e.g., hourly) intervals. However, modeling circadian rhythm with data collected sparsely at irregular intervals and/or data that are not collected at the same time in all individuals has not been reported. The population nonlinear mixed-effects approach can handle such data and also allows covariates to be incorporated into the model. Frequent hourly testosterone concentration data available in the literature for young and elderly healthy volunteers were analyzed first. In the elderly, blunted or completely absent circadian rhythm has been reported, but a full circadian model was significantly better than a model containing one or no circadian component. Therefore, data from both the elderly and young were modeled together, and age was included as a categorical variable (young or elderly). Consistent with literature, the rhythm-adjusted mean testosterone concentrations was lower, and the deviation from the mean, especially to the maximum daily value, was less than half in the elderly (7%) compared to young subjects (16%). The testosterone concentration data measured infrequently and at varying intervals in young normal men and hypogonadal men were evaluated next. Although not measured at regular frequency in each individual, the data were obtained at different clock times for different subjects. Since for population mixed-effects analysis, data from all subjects are pooled, there was enough information to profile the 24-hour circadian cycle. In healthy young subjects, the mean Cnadir, Cpeak, Tnadir, and Tpeak values estimated from the model were 420 ng/dL, 577 ng/dL, 21:42 hours, and 0600 hours, respectively, and were similar to the parameters obtained for the frequently sampled young subjects. In hypogonadal men (testosterone concentrations < 300 ng/dL), the mean testosterone concentrations were much lower than the healthy young or elderly men, and a straight-line model was the best descriptor (i.e., no circadian rhythm was detected). It was also shown that with the application of a transdermal testosterone system, the mean testosterone concentrations in the treated men were within the 95% confidence interval for healthy young men. The results presented here suggest that the advantages of the analysis approach--namely, handling of covariates and handling of sparse, infrequently collected data--can be used in characterizing testosterone circadian rhythm or the lack of it.

Adolescent↗

PubMed2000

The male menopause and mood: testosterone decline and depression in the aging male--is there a link?

The objective of this study was to review the literature on the hormonal changes that occur in aging males in order to determine if testosterone declines in relation to depressed mood and if testosterone might prove useful in treatment of depression. Pertinent articles were identified through a MEDLINE search from 1966 to 1999 and by careful review of the bibliographies of articles most relevant to the topic. There is a moderate decline of total testosterone and more significant decline of bioavailable testosterone in aging males. Elderly males who are depressed appear to have the lowest testosterone levels. In eugonadal males, testosterone replacement does not have a significant effect on mood; in hypogonadal males, some studies show an effect whereas others do not. In several small studies of depressed hypogonadal males, testosterone was effective in alleviating depression. Major side effects of testosterone include increased hematocrit and potential effects on the prostate and lipid metabolism. Testosterone replacement as primary or adjuvant treatment of depression may prove useful in elderly, hypogonadal males who fail to respond to conventional antidepressants. Further studies are needed to confirm these initial impressions.

Aged↗

PubMed1977

Effect of testosterone on compensatory renal hypertrophy in the rat.

The effect of testosterone on compensatory renal hypertrophy (CRH) remains controversial. We therefore examined the effect of exogenous testosterone on CRH in adult male and female rats after unilateral nephrectomy. The influence of endogenous testosterone was studied by comparing the degree of CRH in normal male, castrated male, and in testosterone receptor deficient male pseudohermaphrodite rats. Furthermore, serial determinations of serum testosterone levels were performed after unilateral nephrectomy in male rats. Compensatory renal hypertrophy was comparable between male rats--with or without exogenous testosterone administration--and between normal male, castrated male, and psuedohermaphrodite male rats. In contrast, exogenous testosterone administration in female rats enhanced CRH. Serum testosterone levels fell markedly after unilateral nephrectomy or sham surgery, but increased to 183% and 234% of control values at 1 and 2 days after surgery in the unilaterally nephrectomized rats. At no time, however, did they exceed the range of normal values. The results indicate a different effect of testosterone on CRH in male and female rats.

Animals↗

PubMed1981

Autoregulation of testosterone secretion in perfused rat testes.

Infusion of testosterone into the testicular artery, at concentrations comparable to those that occur in the testicular vein in situ, inhibited LH-stimulated testosterone secretion by rat testes perfused in vitro. This inhibition was rapid and dose responsive. In contrast to testosterone, intra-arterial infusion of 5 alpha-androstan-3 alpha, 17 beta-diol, corticosterone and androstenedione failed to inhibit testosterone secretion. The inhibition of testosterone secretion by intra-arterial infusion of testosterone was reversed by either cessation of testosterone infusion or the simultaneous addition of androstenedione to the artificial perfusion medium. Taken together, these results showed that LH-stimulated testosterone secretion by in vitro perfused rat testes was inhibited by a short-loop negative feedback of testosterone.

Androgens↗

PubMed1981

Serum lipoproteins increase testosterone production in hCG-desensitized Leydig cells.

The effects of high density and low density lipoproteins (HDL and LDL) on testosterone synthesis by Leydig cells from rats treated three days earlier with 50 IU human chorionic gonadotropin (hCG) or from saline-injected control rats were investigated. HDL caused a significant, dose-dependent increase in both basal and hCG-stimulated testosterone production by Leydig cells from hCG-treated rats, but had no marked effect on Leydig cells from control rats. The serum testosterone concentration of hCG-treated rats was three times higher than in controls. Basal testosterone production by Leydig cells from hCG-treated rats was elevated two-fold in comparison to controls, while hCG-stimulated testosterone production was significantly lower than in controls. Both basal and hCG-stimulated testosterone production by Leydig cells from hCG-treated rats were significantly increased by the addition of HDL or LDL. Furthermore, HDL restored the hCG-stimulated testosterone production to the maximal amount produced by hCG-stimulated Leydig cells from control animals. When equivalent amounts of HDL or LDL cholesterol (140 microgram/ml) were added to the incubation, HDL caused a greater increase in testosterone production than did LDL. These results suggest that hCG-treatment, in vivo, caused a prolonged stimulation of the Leydig cells which resulted in depletion of the cholesterol available for steroidogenesis, since the addition of cholesterol in the form of HDL or LDL caused an increase in the testosterone production of these Leydig cells.

Animals↗

PubMed1986

Pulsatile release of luteinizing hormone and testosterone in male ferrets.

The temporal organization of LH and testosterone secretion was examined in male European ferrets. Hormone levels were measured in frequent blood samples taken via an indwelling jugular cannula from sexually mature and castrated ferrets. Intact ferrets discharge LH and testosterone in discrete pulses, but the frequency and amplitude of these pulses vary within and between individual males. The average frequency of LH pulses was 1.14 +/- 0.25 pulses/h, with an amplitude of 1.59 +/- 0.23 ng/ml in 11 ferrets. Testosterone pulse frequency and amplitude were 0.62 +/- 0.04 pulses/h and 16.96 +/- 2.5 ng/ml, respectively. The frequency, amplitude, and duration of hormone pulses were similar during the light and dark phases of the light-dark cycle. LH and testosterone peaks were temporally coupled with LH pulses preceding testosterone pulses by 10-20 min. However, not all LH pulses evoked a rise in testosterone. Frequently, trains of 2 or more LH pulses gave rise to a single testosterone pulse. Castration provoked a rapid increase in the frequency of LH pulses, and the interpulse interval became strikingly uniform within hours after orchidectomy. The amplitude of LH pulses, in contrast, increased gradually over the first 6 postcastration days and then plateaued at about 4.5 ng/ml. These findings demonstrate that LH pulses constitute functionally important signals to the testis, as evidenced by temporally related increments in testosterone secretion. Moreover, distinct differences in the development of the postcastration rise in the frequency and amplitude of LH pulses suggest that testosterone operates via multiple mechanisms to regulate LH release in the adult male. Finally, this study emphasizes the utility of the ferret as an animal model to study neural determinants of LH release in the male.

Animals↗

PubMed1989

Testosterone regulation of proopiomelanocortin messenger ribonucleic acid in the arcuate nucleus of the male rat.

GnRH regulates the secretion of LH and FSH, which stimulate the secretion of testicular hormones. Acting in a reciprocal fashion, these hormones, including testosterone and inhibin, exert a negative feedback effect on GnRH and gonadotropin secretion. Endogenous opioid peptides (EOPs) have been implicated to play a role in steroid-mediated regulation of gonadotropin secretion. In this context, certain steroid hormones (e.g. testosterone) increase EOP activity and ultimately inhibit GnRH secretion; however, the cellular mechanism by which this occurs is unknown. beta-Endorphin is one of these EOPs, and it is derived from a larger precursor molecule, POMC. We tested the hypothesis that testicular hormones and testosterone, in particular, stimulate POMC gene expression in the arcuate nucleus of the male rat brain. First, we compared POMC mRNA levels between intact and castrated male rats. Adult male rats were killed 4 days (n = 4) and 21 days (n = 5) after castration. Intact animals (sham-operated; n = 6) were used as controls. Using in situ hybridization and a computerized image analysis system, we measured the POMC mRNA content in individual cells of the arcuate nucleus. POMC mRNA signal was significantly lower (P less than 0.0003) in both 4-day (126 +/- 2 grains/cell) and 21-day (117 +/- 5 grains/cell) castrates than in controls (142 +/- 2 grains/cell). In a second experiment we tested whether testosterone would reverse the castration-induced loss of POMC message. Again, we castrated animals and immediately implanted them with either empty (sham; n = 6) or testosterone-containing Silastic implants (n = 5) of a size that would deliver physiological levels of testosterone (3.6 +/- 1.5 ng/ml). We observed that testosterone-treated animals had significantly higher levels of POMC mRNA signal (121.8 +/- 3.8 grains/cell) than sham-treated castrates (111.4 +/- 3.6 grains/cell; P less than 0.03) and that the testosterone-treated castrates had POMC mRNA signal levels indistinguishable from those of intact controls (122.0 +/- 1.1 grains/cell). These observations lend credence to the theory that one mechanism by which testosterone may regulate GnRH secretion is by increasing the synthesis of POMC in the arcuate nucleus.

Animals↗

PubMed1989

Regional specificity of testosterone regulation of proopiomelanocortin gene expression in the arcuate nucleus of the male rat brain.

Endogenous opioid peptides have been implicated as mediators in the negative feedback action of gonadal steroids on GnRH secretion. We have previously demonstrated that testosterone stimulates POMC gene expression in neurons of the arcuate nucleus. However, the wide distribution and variety of actions attributed to the numerous arcuate POMC neurons suggest that these cells may be heterogeneous in their responsiveness to steroid hormones. We tested the hypothesis that testosterone modulates a select population of POMC neurons within the arcuate nucleus of the adult male rat by comparing POMC mRNA signal levels throughout the arcuate nucleus of intact, castrated, and castrated testosterone-replaced adult males. Adult male rats were castrated and implanted (sc) with a Silastic capsule (30 mm) that was either empty (n = 6) or filled with crystalline testosterone (n = 5). Control sham-operated animals (n = 6) were left intact. In each animal the arcuate nucleus was divided into four equal rostral-caudal areas within which we measured POMC mRNA content in individual cells. We report that the effects of castration and testosterone replacement are observed in POMC neurons located in the most rostral region of the arcuate nucleus. After castration, POMC mRNA content was reduced in cells of the most rostral arcuate area (intact, 152 +/- 5 grains/cell; castrate, 119 +/- 2 grains/cell; P less than 0.0005), and replacement with physiological levels of testosterone prevented the decline in POMC mRNA levels so that they remained equivalent to that of the intact animal (castrated testosterone-replaced, 153 +/- 6 grains/cell). There was no significant difference in POMC mRNA signal between intact and castrated testosterone-replaced animals in the most rostral area. POMC neurons in the more caudal aspect of the arcuate (75% of the nucleus) were unaffected by the treatments; alternatively, it is possible that a real change in POMC message content in a subpopulation of cells was obscured by larger numbers of nonresponding cells within the same tissue sections. Based on these observations we conclude that there is a heterogeneous population of POMC neurons in the arcuate nucleus and that testosterone regulates POMC gene expression in a select group of these cells located in the rostral portion of the arcuate nucleus.

Animals↗

PubMed1989

Conservation of free but not total or non-sex-hormone-binding-globulin-bound testosterone in serum from Nagase analbuminemic rats.

Nagase analbuminemic rats have normal reproductive capacity, normal apparent libido, and normal serum concentrations of LH and FSH. Therefore, it is reasonable to assume that intracellular sex steroid hormone concentrations are normal or at least adequate to maintain normal reproductive function in these rats. To test whether intracellular testosterone concentrations in these rats are maintained by the circulating concentration of free or free-plus-weakly-bound testosterone, we measured the concentrations of total testosterone, free testosterone, and non-sex-hormone-binding-globulin-bound testosterone in sera from five adult male Nagase analbuminemic rats and from five age- and sex-matched controls. We found that the analbuminemic rats had markedly decreased serum concentrations of total and non-sex-hormone-binding-globulin-bound testosterone, but normal serum concentrations of free testosterone. These results suggest that intracellular concentrations of testosterone in biologically relevant organs of the rat are maintained by the concentration of free rather than free-plus-weakly-bound testosterone in plasma, in accord with the free hormone hypothesis.

Animals↗

PubMed1992

Exogenously administered testosterone maintains spermatogenesis quantitatively in adult rats actively immunized against gonadotropin-releasing hormone.

The administration of testosterone via Silastic capsules has been shown previously to maintain advanced spermatid number quantitatively in intact rats in which LH but not FSH was suppressed, but not in hypophysectomized rats, indicating that pituitary factors in addition to LH are required for the quantitative maintenance of spermatogenesis in the rat. The objective of the present study was to examine whether testosterone is capable of maintaining quantitatively normal spermatogenesis in rats in which both LH and FSH are suppressed. Intact adult male rats were actively immunized against GnRH by intradermal injection of GnRH conjugated to human serum globulin; control rats received intradermal injections of saline and adjuvant. Four weeks after the primary immunization, GnRH-immunized rats received the first booster injection and, at the same time, received testosterone-filled polydimethylsiloxane (PDS) implants of 4, 8, 12, or 24 cm or empty implants. Booster injections were repeated every 2 weeks for 8 weeks. At that time, rats were killed, and serum levels of LH, FSH, and testosterone, testicular advanced spermatid number, and seminiferous tubule fluid testosterone concentrations were determined. Four weeks after the initial administration of GnRH immunogen, i.e. before the first booster injection, serum levels of testosterone, LH, and FSH and the number of advanced spermatids per testis were not different from those in controls. Eight weeks after the first booster injection, serum LH and FSH and advanced spermatids were undetectable in all GnRH-immunized rats. The administration of testosterone-filled PDS implants of 4 and 8 cm to GnRH-immunized rats for 8 weeks resulted in the maintenance of 105 +/- 6 and 161 +/- 5 x 10(6) advanced spermatid/testis, respectively, significantly less than the control value (237 +/- 19 x 10(6)). In GnRH-immunized rats that received testosterone-filled PDS implants of 12 or 24 cm, the advanced spermatid numbers per testis (228 +/- 4 and 229 +/- 8 x 10(6), respectively) were not significantly different from those in controls. These results indicate that testosterone is capable of maintaining spermatogenesis quantitatively in the adult rats testis, in the absence of both radioimmunoassayable LH and FSH.

Animals↗

PubMed1993

Receptor-mediated stimulatory effect of atrial natriuretic factor, brain natriuretic peptide, and C-type natriuretic peptide on testosterone production in purified mouse Leydig cells: activation of cholesterol side-chain cleavage enzyme.

We have investigated the mechanism by which different natriuretic peptides stimulate steroidogenesis in purified mouse Leydig cells. In addition to atrial natriuretic factor (ANF), we show that brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) also stimulate testosterone production in these cells. Testosterone production was increased dramatically to 14-fold with ANF (EC50 = 0.3 nM) and 15-fold with BNP (EC50 = 0.2 nM); however, the CNP-stimulated level of testosterone production was only 2.5-fold compared with controls. ANF and BNP enhanced the stimulatory effect of LH on testosterone production. The C-ANF(4-23) (a truncated form of ANF) had no effect on testosterone production in these cells. ANF, BNP, and CNP stimulated the production of intermediate precursors of testosterone biosynthesis, which included progesterone, 17 alpha-hydroxy progesterone, androstenedione, pregnenolone, 17 alpha-hydroxy pregnenolone, and dehydroepiandrosterone sulfate. The conversion of pregnenolone and progesterone to testosterone was also significantly enhanced after treatment of Leydig cells with these peptides. All three natriuretic peptides (ANF, BNP, and CNP) stimulated the activity of particulate guanylate cyclase by 8.4-, 8.5-, and 4.8-fold and the accumulation of intracellular cGMP by 52-, 58-, and 19-fold, respectively. The cGMP inhibitor LY83583 attenuated both the generation of cGMP as well as testosterone in response to these natriuretic peptides, suggesting the involvement of cGMP as a second messenger. Leydig cells were found to contain high affinity and low capacity binding sites for ANF [dissociation constant (Kd), 2.0 x 10(-10) M; maximum binding capacity (Bmax). 20 fmol/1 x 10(5) cells], BNP (Kd, 2.2 x 10(-10) M; Bmax, 19 fmol/1 x 10(5) cells), and CNP (Kd, 3.1 x 10(-10) M; Bmax, 8.6 fmol/1 x 10(5) cells). The results presented here document that a family of different natriuretic peptides stimulates Leydig cell steroidogenesis in receptor-mediated fashion, beginning at the cholesterol side-chain cleavage enzyme. The data also show that these peptide hormones induce testosterone production in mouse Leydig cells by involving both delta 4- and delta 5-pathways of steroidogenesis.

Animals↗