Biomedical subjects

P Troen

Publications and source records attributed to P Troen.

At least 37 records · Page 2Linked to original sources

PubMed1988

Alpha-subunit secretion in men with idiopathic hypogonadotropic hypogonadism.

We studied the regulation of glycoprotein hormone alpha-subunit secretion in four men with idiopathic hypogonadotropic hypogonadism due to presumed GnRH deficiency. Immunoreactive alpha-subunit was present at low but usually detectable levels in blood samples drawn at 10- to 20-min intervals for 12-24 h; however, no characteristic pattern of pulsatile alpha-subunit secretion was found. Serum from each man was examined by gel filtration chromatography. Each sample tested contained an immunoreactive alpha-subunit peak with a slightly lower elution volume than [125I]hCG alpha, as we had previously found in serum from normal men. To determine if this peak represented TSH alpha, two men were treated with 0.3 mg L-T4 daily for 7-14 days. Serum TSH levels decreased to less than 1.5 mU/L, and neither TSH nor alpha-subunit levels increased after the iv administration of 500 micrograms TRH. An alpha-subunit peak that eluted before [125I]hCG alpha was again found in the serum of T4-treated men. We conclude that glycoprotein hormone alpha-subunit is present in the serum of men with idiopathic hypogonadotropic hypogonadism in whom TSH secretion is completely suppressed by L-T4. The gonadotrophs represent the most likely source of this alpha-subunit. The finding of more normal alpha-subunit than LH secretion in these men indicates that the production of the gonadotropin subunits is differentially regulated in man and supports the hypothesis that factors in addition to GnRH regulate alpha-subunit gene expression.

Adult↗

PubMed1987

Identification of inhibin secreted by cynomolgus monkey Sertoli cell cultures.

An inhibin was identified in the media of primary Sertoli cell-enriched cultures from the cynomolgus monkey, Macaca fascicularis, and some of its biochemical properties were studied. Conditioned monkey Sertoli cell culture medium (m-SCCM), when added to pituitary cells from 6-week-old male rats, inhibited the basal secretion of FSH but not that of LH. This specificity was lost after the addition of GnRH; mSCCM inhibited not only FSH but also LH release, determined by both RIA and mouse interstitial cell bioassay, from pituitary cells exposed for 6 h to 10 nM GnRH. FSH-inhibiting activity persisted when m-SCCM was boiled for 30 min, but activity was lost after incubation for 1 h at 37 C with 0.1% trypsin. m-SCCM inhibin activity was completely retained by Concanavalin A-Sepharose and could be eluted with 0.2 M alpha-methyl-D-glucoside. Gel filtration high pressure liquid chromatography with a Superose-12 column revealed inhibin activity between 20-60K, with the greatest activity at 40K. Our results indicate that primate Sertoli cells produce an inhibin-like factor which could play a role in controlling gonadotropin secretion in males.

Animals↗

PubMed1986

Assay of primate seminiferous tubule androgen receptors using [3H]mibolerone.

The synthetic radiolabelled androgen mibolerone (7 alpha, 17 alpha-dimethyl-19-nortestosterone) was used to characterize androgen receptor binding in the seminiferous tubules from Cynomolgus monkey testis. Mibolerone binding was of high affinity (Kd = 0.6-5.4 nM) and limited capacity (37-50 fmol/mg protein), and was androgen specific. Sucrose density gradient centrifugation using a vertical tube rotor permitted the identification of a 9S molybdate-stabilized receptor under low salt conditions. The receptor bound to DEAE-cellulose. Methyltrienolone, but not mibolerone, also bound to a low affinity high capacity binding site in tubule cytosol, which probably represents glucocorticoid receptor binding, since it could be displaced by excess dexamethasone. However, occupancy of this low-affinity binding site by dexamethasone in an androgen receptor assay with [3H]methyltrienolone lead to a 33% underestimation of receptor binding, which appeared to relate to radioactive decomposition. Mibolerone, as well as methyltrienolone, bound to a progestin-binding protein in seminiferous tubule cytosol. These studies provide methods for the study of seminiferous tubule androgen receptors in subhuman primates and indicate that, due to its greater stability and lack of binding to glucocorticoid receptor, mibolerone is a useful new ligand in the study of androgen receptors in testis and its constituent cells.

Animals↗

PubMed1986

Testosterone and estradiol are co-secreted episodically by the human testis.

In spite of a striking pulsatile pattern of luteinizing hormone (LH) secretion, testosterone (T) fluctuations in peripheral blood in normal adult men are irregular and of low amplitude. To determine whether T secretion by the human testis is episodic, T was measured in blood samples drawn at 15-min intervals for 4 h through a catheter placed in the testicular vein of six men with varicocele-associated infertility. Estradiol (E2) concentrations were also determined in each sample. Each subject released testosterone in well-defined pulses. Gonadal vein T levels ranged from 1 to 1,540 ng/ml. Mean (+/- SE) pulse amplitude was 176 +/- 42 ng/ml, with a frequency of 4.0 +/- 0.3 pulses per 4 h. Testicular vein E2 levels ranged from 0.01 to 6.8 ng/ml. E2 secretory episodes were generally coincident with T pulses, and their amplitudes were highly positively correlated (r = 0.90, P less than 0.01). These results indicate that T secretion by the adult human testis is pulsatile, and suggest a functional relationship between intermittent LH secretion and normal testicular steroidogenesis in men. The failure to appreciate these fluctuations as hormone pulses in peripheral blood may relate to their absolute amplitude and frequency. The concordance between E2 and T pulses suggests that the Leydig cell, under LH control, is the source of most of the E2 secreted by the adult human testis.

Adult↗

PubMed1986

Testicular control of prostaglandin E2 production in rat vas deferens.

Orchidectomy decreased and testosterone (T) replacement restored prostaglandin E2 (PGE2) concentrations in adult rat vas deferens. To explain this finding, phospholipase A (PLase-A) and PG synthetic activity were studied in vas tissue from 9-week-old rats orchidectomized with or without T replacement as well as in rats in which the cauda epididymidis was ligated. PG synthetic activity fell to 3% of intact levels in 14-day castrate rats and was restored to normal by T replacement. Although vas PLase-A activity was also significantly (P less than 0.01) reduced to 38% of the control level in 14-day castrate rats, this change appears in part to reflect a castration-related increase in endogenous phospholipid concentrations. Further, T replacement only partially restored PLase-A activity to 59% of intact levels. Ligation of the cauda epididymidis in intact rats reduced vas PLase-A activity to castrate levels without altering vas T concentration. These results demonstrate both a direct effect of T on the biosynthesis of PGs in rat vas deferens as well as a paracrine effect, which appears to be mediated by a factor(s) other than T. These data suggest the existence of a new mechanism through which testicular products contribute to the function of the vas deferens.

Animals↗

PubMed1985

Studies of the human testis. XX--Effect of NADH on 17 alpha-hydroxypregnene C17-20 lyase activity.

A study of the cofactor requirements of C17-20 lyase was carried out using human testis tissue obtained at the time of orchiectomy for treatment of prostatic carcinoma. Washed microsomal fractions were prepared from frozen human testes using a KCl containing buffer. The preparation revealed dose-dependent activity of C17-20 lyase in the presence of either NADPH or commercial or purified NADH. The Km of NADH for the enzyme was of the order of 10(-3) M and the Km of NADPH was determined as 1.6 X 10(-5) M. NADH also provided synergistic enhancement of NADPH-mediated lyase activity, and decreased the Km of NADPH for the lyase but did not change the Vmax of NADPH-mediated lyase activity. Carbon monoxide inhibited both NADH and NADPH-mediated lyase activities indicating that both activities are catalyzed by cytochrome P-450. Cations including Ca2+, Mg2+ and Mn2+ were found to inhibit the NADPH-mediated lyase activity but enhanced the lyase activity in the presence of NADH. The results indicate both the presence of NADH-mediated C17-20 lyase activity and the synergistic effect of NADH on NADPH-mediated lyase activity in the human testis.

Aged↗

PubMed1985

An analysis of the age-related decline in testicular steroidogenesis in the rat.

The effect of aging in rats on serum and intratesticular testosterone levels, microsomal steroidogenic enzyme activities and microsomal cytochrome P-450 was studied. Serum testosterone levels were highest in 11-wk-old rats, declined at age 16 wk and further declined between ages 7 and 21 mo. Intratesticular testosterone levels in 21-mo-old rats were significantly lower than those of the other groups. The activity of 17 alpha-hydroxylase and C17-20 lyase, as well as cytochrome P-450, decreased significantly in 21-mo-old rats. The activity of 17 beta-hydroxysteroid oxidoreductase increased from 11 wk to 16 wk of age and then declined by 21 mo of age to the levels of 11-wk-old animals. Similar changes in delta 5-3,3-hydroxysteroid dehydrogenase coupled with delta 5-delta 4 isomerase activities were observed, but were not statistically significant. These results suggest that the decline in testosterone production in old rats is predominantly a result of decreased oxygenase activity. Inasmuch as oxygenases are gonadotropin dependent, our results support the hypothesis that gonadotropin deficiency is the major factor responsible for Leydig cell dysfunction in old rats. Further, the decline in the ratio of 17 alpha-hydroxylase to C17-20 lyase with aging suggests that other factors affect these enzymes as well as the reduction in cytochrome P-450.

Aging↗

PubMed1985

Identification of androgen-binding protein from testis cytosol and sertoli cell culture medium of the cynomolgus monkey, Macaca fascicularis.

The biochemical and immunological properties of monkey androgen-binding protein (mABP) from the cynomolgus monkey, Macaca fascicularis, have been examined in testis cytosol and medium of primary Sertoli cell-enriched cultures. mABP in testis tissue was separated from the serum protein testosterone-estradiol-binding globulin (mTeBG) by affinity chromatography on Concanavalin A-Sepharose (Con A). mTeBG from serum extracts was completely retained by the lectin and could be displaced with buffer containing alpha-methyl-D-glucoside. In contrast, mABP from testis extracts either did not interact with the Con A and appeared in the void volume or was partially retained by the column and could be eluted with buffer alone. A third component retained by the Con A may represent mTeBG contamination, a form of mABP which binds to Con A, or both. The specific 5 alpha-dihydrotestosterone (DHT)-binding activity in the void volume of the Con A column was designated mABP and was further studied. [3H]DHT binding to mABP was saturable and of limited capacity (0.163 +/- 19 pmol/mg protein). Scatchard analysis of the data was consistent with a single class of binding sites with an apparent dissociation constant (Kd) at 4 C of 2.6 +/- 0.2 X 10(-9) M. DHT was the most effective competitor of [3H]DHT binding to mABP, followed by 2-methoxyestradiol, testosterone, estradiol, and cyproterone acetate. Concentrated Sertoli cell culture medium subjected to steady state polyacrylamide gel electrophoresis produced a single peak of specifically bound [3H]DHT with a mobility similar to that of other androgen-binding proteins. [35S]Methionine-labeled medium proteins were immunoprecipitated with a rabbit anti-human TeBG antiserum. Two bands, corresponding to mol wt of approximately 46,000 and 48,000, were observed by fluorography, with the lighter component being more intense. After androgen affinity chromatography of radiolabeled medium proteins, these two bands were again observed on sodium dodecyl sulfate-urea-containing polyacrylamide gels. These results demonstrate that 1) mABP may be separated from mTeBG by lectin affinity chromatography, as in humans; 2) hTeBG and mABP are antigenically related; and 3) mABP consists of subunits of different mol wt in unequal ratios.

Androgen-Binding Protein↗

PubMed1985

Pulsatile secretion of immunoreactive alpha-subunit in man.

We compared the secretion of uncombined alpha-subunit with LH secretion, as measured by RIA in six normal men, an agonadal adult man, and an adult woman with testicular ferminization. Blood samples were drawn every 10 min for 12 h to evaluate pulsatile LH and free alpha secretion. Spontaneous alpha pulses occurred every 120 +/- 60 min (mean +/- SD; range, 40-260) in eugonadal men. The mean alpha pulse amplitude was 0.49 +/- 0.11 ng/ml, representing an increase of 60 +/- 18% above the preceding nadir value. alpha pulses were generally associated with LH pulses, and the amplitudes of concordant alpha and LH pulses were highly positively correlated (r = 0.58; P less than 0.01). The absolute amplitude of concordant alpha peaks was 1.5 +/- 0.7% that of corresponding LH peaks. Additional alpha pulses were noted in each subject for which simultaneous LH fluctuations failed to meet the criteria for pulses. Studies in the agonadal man and in the patient with testicular feminization revealed that the frequency of both spontaneous alpha and LH pulses was increased to approximately twice that in normal men. Gel filtration analysis indicated that all alpha radioimmunoactivity in normal male sera coeluted with [125I]alpha. By contrast, in hypogonadal sera, only 50-60% of alpha immunoreactivity coeluted with [125I]alpha, the remaining activity appeared in the region of LH and FSH and resulted from RIA cross-reactivity. We conclude that uncombined alpha-subunit, as well as LH is normally released into the peripheral blood in discrete pulses. In the absence of exposure to androgen, the frequency of these pulses increases, presumably as a consequence of the accelerated release of LRH. However, alpha RIAs overestimate the concentration of uncombined alpha in hypogonadal sera. We propose that the coanalysis of LH and alpha secretory episodes may prove useful in resolving some of the complexities associated with gonadotropin secretory patterns.

Adult↗

PubMed1985

Evidence for a role of endogenous estrogen in the hypothalamic control of gonadotropin secretion in men.

To examine the mechanism by which endogenous estrogens inhibit gonadotropin secretion in men, blood samples were drawn every 10 min for 12 h in five men before and at the completion of 3 weeks of treatment with the estrogen antagonist clomiphene citrate (50 mg twice daily). Samples were analyzed for LH and alpha-subunit by RIA. Clomiphene produced a 3-fold rise in circulating LH levels, which was associated with a 80% increase in pulse frequency and a 70% increase in pulse amplitude. Immunoreactive alpha-subunit secretion was also pulsatile before and after clomiphene treatment. Mean alpha-levels rose 70%, together with a 39% increase in pulse frequency and a 41% increase in pulse amplitude. Circulating testosterone and estradiol levels increased 2-fold and FSH levels increased 3-fold after clomiphene treatment. Insofar as each LH and uncombined alpha-subunit pulse reflects a LHRH secretory episode, our data indicate that endogenous estrogens tonically restrain the hypothalamic release of LHRH. From these results and those of previous studies, we conclude that estrogens as well as androgens are important in the testicular feedback inhibition of the hypothalamic oscillator that governs pulsatile gonadotropin secretion.

Adult↗

PubMed1985

Studies of the human testis. XIX. Preparation of an antibody to human testosterone-oestradiol-binding globulin and its application to the study of testicular androgen-binding protein.

Human testosterone-oestradiol-binding globulin (hTeBG) was purified from pregnancy serum by ammonium sulphate precipitation, preparative flatbed electrofocusing, Concanavalin A-Sepharose affinity chromatography, Sephadex G-150 gel filtration, DEAE-Sephadex chromatography and preparative polyacrylamide gel electrophoresis. The yield was 0.3 mg of hTeBG with a specific acitivity of 1.1 nmoles DHT bound per mg. An antiserum to TeBG was raised in rabbits. Anti-hTeBG IgG was separated from rabbit TeBG by DEAE-Affi-Gel-Blue chromatography. Anti-hTeBG was titrated using protein A-Sepharose which quantitatively binds IgG and therefore bound [3H]DHT-hTeBG-anti-TeBG complexes. The androgen binding components from human testis were separated on Concanavalin A-Sepharose columns into excluded and retained fractions. The antibody bound both testis fractions with titration curves which paralleled that of TeBG, indicating that these androphilic proteins share common immunodeterminants with hTe-BG. The possibility that these testicular proteins are identical in amino acid sequence to TeBG and differ only in carbohydrate content will require further verification. Finally, these results indicate that antibodies to TeBG can be used to study human testicular androgen-binding protein.

Androgen-Binding Protein↗

PubMed1984

Steroidogenesis in the monkey testis: relationship of enzyme organization to endogenous steroids, steroidogenesis and gonadotropin treatment.

To explore testicular factors which determine steroidogenesis, circulating and intratesticular steroid levels were measured and in vitro steroidogenesis in testicular mines and microsomes was investigated using adult rhesus monkeys before and after treatment with pharmacological doses of hCG or hCG together with hMG. After gonadotropin treatment serum and intratesticular levels of 17 alpha-hydroxyprogesterone as well as end product testosterone were markedly elevated. Dynamic studies revealed that 17 alpha-hydroxyprogesterone produced from pregnenolone was partly metabolized to C19-steroids but almost no 17 alpha-hydroxyprogesterone produced from progesterone was utilized by C17-20 lyase. Androstenedione levels increased in serum after both treatments and were elevated in testis tissue after hCG treatment. Androstenedione accumulated in vitro during incubation of untreated and hCG-treated testes with [3H]pregnenolone and [14C]progesterone. The major portion of the accumulated androstenedione was produced from pregnenolone through dehydroepiandrosterone rather than through 17 alpha-hydroxyprogesterone, indicating differential availability of androstenedione to 17 beta-hydroxysteroid oxidoreductase according to its origin. The 3H/14C ratio in product androstenedione was much greater than the ration in product testosterone in both untreated and hCG-treated testis; in testes of animals treated with hCG together with hMG, the ratios in both products were closely linked. Among the enzymes examined, 17 alpha-hydroxylase and C17-20 lyase activities for 5-ene-C21-steroids were increased and 17 beta-hydroxysteroid oxidoreductase activity were decreased by gonadotropin treatment. Our findings confirm the phenomenon of unequal substrate availability to enzymes depending upon the provenance of the substrate and demonstrate that gonadotropin(s) change substrate availability as do direct changes in enzyme activities. The unequal substrate availability validates the assumption, previously proposed by others, that microsome enzymes have an organized arrangement as enzyme complexes.

Animals↗

PubMed1984

Evidence for an androgen receptor in the seminiferous tubules of the human testis.

Androgen receptors (AR) were studied in seminiferous tubule cytosol and testicular nuclear extracts prepared from testes of previously untreated elderly men undergoing orchiectomy as therapy for prostatic carcinoma. Cytosol exhibited high affinity (Kd = 0.8 nM), saturable binding of [3H]methyltrienolone; however, the synthetic progestin, promegestone was a stronger competitor for MT binding sites than were 5 alpha-dihydrotestosterone (DHT) or testosterone (T), suggesting the presence of progesterone-like binding sites. Addition of triamcinolone acetonide (TA) produced the usual relative steroid specificity for AR binding and reduced the measured AR binding capacity by 19 +/- 8% (Mean +/- SD, n = 3). The umber of MT binding sites was 30-40 fmol/mg protein, or an average of 65 fmol/g testis, and the equilibrium dissociation constant at 0 degrees C was 0.6-1.4 nM. In the presence of sodium molybdate, binding was stable for 40 h at 0 degrees C and the half-time of dissociation of the MT-AR complex was 12-16 h. The binding of salt extractable (600 mM KCl) nuclear sites to MT was saturable and was specific for androgens. The number of binding sites in nuclear extracts was 170 fmol/g testis and the apparent equilibrium dissociation constant was 4.2 nM. Thus, the binding of MT to human seminiferous tubule cytosol and testicular nuclear extract exhibits properties which are nearly identical to those of the prostate AR. Further study of this androphilic protein may provide insight into the role of androgen in normal and abnormal spermatogenesis in man.

Cell Nucleus↗

PubMed1984

The gonadotropin-suppressive activity of androgen is increased in elderly men.

The influence of aging on the responsiveness to sex steroid hormones in men was studied by comparing circulating gonadotropin concentrations, pulsatile LH release, and sex hormone-binding globulin (TeBG) levels. This was done before and during a four-day continuous infusion of testosterone (T) (7.5 mg/d), dihydrotestosterone (DHT) (7.0 mg/d), or estradiol (E2) (45 micrograms/d) in young adult men, ages 18 to 32, and healthy elderly men, ages 65 to 80. DHT reduced mean serum LH and FSH levels as well as the frequency of spontaneous LH secretory episodes to a greater extent (p less than 0.05) in old men than in young men. T administration also reduced serum LH levels more in aged than in young men (P less than 0.05); however, this difference was less pronounced than for DHT. During T infusion, the decrease in serum FSH levels was similar in the two groups. Spontaneous LH pulse amplitude also declined during both T and DHT infusion in aged, but not in young men. By contrast, infusion of E2 reduced both serum LH and FSH levels comparably in aged and young men. DHT infusion also reduced serum TeBG levels equally in old and young men. Finally, each steroid infusion produced comparable mean circulating levels of T, DHT, and E2 in both groups. These data indicate that elderly men are more responsive than are young men to the gonadotropin-suppressive effects of androgen, but not to DHT effects on circulating TeBG levels. The more pronounced deceleration of spontaneous LH secretory episodes during DHT infusion in aged men provides evidence for an alteration in hypothalamic function in male senescence.

Aged↗

PubMed1984

Basal and adrenocorticotropic hormone-stimulated serum 17 alpha-hydroxyprogesterone in men with idiopathic infertility.

Basal serum 17 alpha-hydroxyprogesterone (17-OHP) concentrations and the 17-OHP response to acute adrenocorticotropic hormone administration were studied in infertile men with idiopathic oligospermia to determine the prevalence of attenuated 21-hydroxylase deficiency. Mean (+/- standard error of the mean) basal serum 17-OHP levels in 50 infertile men (1.17 +/- 0.06 ng/ml) and 25 normal volunteers (1.09 +/- 0.08 ng/ml) were indistinguishable (not significant). However, two infertile men had 17-OHP levels which were above the normal range. Following the intravenous administration of 0.25 mg of synthetic adrenocorticotropic hormone (cosyntropin) to these two men and to eight additional infertile men, the mean increase in 17-OHP concentrations was 0.84 +/- 0.15 ng/ml, a response which was similar to that of normal men (0.94 +/- 0.26 ng/ml). No patient demonstrated the minimum fourfold rise in 17-OHP previously reported in men with attenuated 21-hydroxylase deficiency, suggesting the absence of this disorder among these subjects. This study suggests that subtle 21-hydroxylase deficiency is rare among infertile men with idiopathic infertility.

17-alpha-Hydroxyprogesterone↗

PubMed1984

Altered pulsatile secretion of luteinizing hormone in hypogonadal men with hyperprolactinaemia.

To explore the mechanism for the hypogonadism associated with prolactin hypersecretion in men we examined luteinizing hormone (LH) secretory profiles in four hyperprolactinaemic men before and during treatment with bromocriptine. Pretreatment serum prolactin levels were increased 4-100 fold and serum testosterone levels were low in three men and low-normal in the fourth subject. Mean LH levels were low-normal and the frequency of spontaneous LH secretory episodes was less than normal in three of four men. Bromocriptine reduced serum prolactin levels to normal; subsequently, serum testosterone levels increased and libido and potency improved markedly in each man. The rise in serum testosterone levels was associated with an increase in mean LH concentrations and in LH pulse frequency. Mean follicle-stimulating hormone levels also increased during bromocriptine treatment. Insofar as each LH pulse is believed to reflect a discharge of gonadotrophin releasing hormone from the anterior hypothalamus, our data suggest that a major abnormality in hyperprolactinaemic men with hypogonadism is a disorder of the neuroregulatory mechanism for pulsatile gonadotrophin-releasing hormone secretion.

Adult↗

PubMed1983

Studies of the human testis. XVIII. Simultaneous measurement of nine intratesticular steroids: evidence for reduced mitochondrial function in testis of elderly men.

To determine the basis for the decline in testosterone production by the aged testis, intratesticular unconjugated steroids, including testosterone, pregnenolone (3 beta-hydroxy-5-pregnen-20-one), 17 alpha-hydroxypregnenolone (3 beta,17 alpha-dihydroxy-5-pregnen-20-one), dehydroepiandrosterone (3 beta-hydroxy-5-androsten-17-one), androstenediol (5-androstene-3 beta,17 beta-diol), progesterone, 17 alpha-hydroxyprogesterone, androstenedione (4-androstene-3,17-dione), and 17 beta-estradiol, were measured by simultaneous RIAs in 32 previously untreated elderly men (aged 61-85 yr) undergoing orchiectomy as therapy for prostatic carcinoma and 20 young men (aged 25-35 yr) with oligospermia and varicocele. In vitro steroidogenesis using labeled pregnenolone as substrate was also investigated. Serum and intratesticular testosterone levels were lower (P less than 0.05) in aged patients [3.3 +/- 1.9 ng/ml and 0.86 +/- 0.53 microgram/g tissue (mean +/- SD)] than in young men (6.4 +/- 1.9 ng/ml and 1.7 +/- 1.1 microgram/g tissue), while circulating LH levels were higher (P less than 0.05) in elderly men (151 +/- 105 ng/ml) than in the young men (79 +/- 33 ng/ml), indicating that a primary pathological process affects the senescent testis, producing a decline in testosterone production. Study of bioconversion of [3H]pregnenolone to delta 4 steroids, 17 alpha-hydroxysteroids, and C19 steroids as well as analysis of the relative amounts of intratesticular steroids, as determined by RIA, revealed no apparent differences in the process of microsomal steroidogenesis in elderly compared to that in young men. The sum of the nine measured intratesticular steroid concentrations per g tissue wt was significantly lower (P less than 0.05) in aged patients (1.94 +/- 0.93 microgram/g tissue), than in young patients (3.68 +/- 1.90 micrograms/g tissue). The sum of the nine intratesticular steroids measured was positively correlated (P less than 0.01) with circulating LH levels in both patient groups, and the slope of this regression line was 14-fold greater for young men than for elderly men. Since the total concentration of the nine measured steroids reflects the pregnenolone supplied by the mitochondria within Leydig cells, it appears that the decline in Leydig cell function in aged men is attributable to a reduced supply of mitochondrial steroid precursors rather than to an impairment in microsomal steroidogenesis.

Adult↗

PubMed1983

A reexamination of pulsatile luteinizing hormone secretion in primary testicular failure.

The pulsatile pattern of LH secretion was studied in six patients with primary testicular failure and six healthy adult men by drawing peripheral blood samples every 10 min for 12 h. Mean basal LH concentrations were increased approximately 6-fold in hypogonadal men. In these patients mean absolute LH pulse amplitude was 3 times that of the controls [106 +/- 27 (SE) ng/ml vs. 31 +/- 2 ng/ml; P less than 0.01] and the frequency of spontaneous LH secretory episodes was increased 2-fold (between-pulse interval of 53 +/- 3 min vs. 107 +/- 8 min; P less than 0.01). Mean pulse amplitude was directly related to mean LH concentration in hypogonadal men (r = 0.94, P less than 0.01), but not in controls (r = 0.38, P = NS). Within each group there was no relationship between circulating testosterone or mean LH levels and LH pulse frequency. This study demonstrates that the increased circulating levels of LH in hypogonadal men are a consequence of an increase in both LH pulse frequency and pulse amplitude. The prolonged, more frequent sampling protocol used revealed a pattern of LH secretion not evident in previous studies. Finally, these data provide further, albeit indirect, evidence that androgens may regulate the intermittent release of LHRH in man.

Adult↗