Spermatic Venous Plasma Research Articles

Secretion by the human testis of epitestosterone, with its sulfoconjugate and precursor androgen 5-androstene-3β,17α-diol

Epitestosterone (ET) and testosterone (T), free and sulfoconjugated, as well as 5-androstene-3β,17α-diol (5AD3β17α) and its 17β-epimer have been analyzed, by gas chromatography-mass spectrometry with stable isotope dillution, in peripheral and spermatic venous plasma of patients with left varicocele. All these androgens are secreted by the testis as evidenced by the significant concentration gradients between peripheral and spermatic venous plasma. Half of the daily ET production is ascribed to the testis, while 95% of T sulfate and roughly 70% of ET sulfate are also of testicular origin. Significant correlations between ET and 5AD3β17α are an indication that the 5-ene pathway is also operative for ET biosynthesis. High ratios of spermatic to peripheral venous plasma levels of ET and 5AD3β17α are also related to the high clearance rates of 17α-hydroxy-androgens.

The form and function of the Leydig cells in hypophysectomized rams treated with pituitary extract when spermatogenesis is disrupted by heating the testes

The morphology and in-vivo function of the Leydig cells were studied in rams when spermatogenesis had been disrupted by a single exposure of the testes 20 days earlier to a temperature of about 42 degrees C for 45 min. To avoid complications due to changed negative feedback from the testes to the pituitary with consequent changes in the degree of gonadotrophic stimulation, ten of the animals (five heated and five unheated) were surgically hypophysectomized when the testes were heated and then treated twice daily with pituitary extract. Six intact rams (three heated and three unheated) were also studied. The heat-affected testes were about half the size of the unheated testes, and blood plasma flow was closely related to testis weight. There were no differences in the testosterone concentrations in spermatic venous blood, testicular lymph or rete testis fluid, or in oestradiol in spermatic venous plasma from heated or unheated testes. Consequently, testosterone secretion by the heat-affected testes was markedly reduced, and the concentrations in jugular blood were also lower in the heat-affected rams than in controls. The volume of the interstitial tissue was less in absolute terms in the heat-affected rams, but it made up a greater fraction of the testes. The absolute volume of the blood plus lymph vessels, and their fraction of the interstitial tissue were lower in the heat-affected testes, although there was no effect on their volume as a fraction of the whole testis. The heat-affected testes of the hormone-treated rams had fewer Leydig cells, but each cell was larger; no equivalent difference was found in the intact rams. However, the dose of pituitary extract chosen was somewhat excessive, as there were higher than normal concentrations of FSH, LH and testosterone in jugular blood plasma, of testosterone and oestradiol in testicular venous blood plasma and of testosterone in rete testis fluid in the hormone-treated hypophysectomized rams. The testes of the unheated hypophysectomized rams increased in size by about 20% during treatment with pituitary extract, although testicular blood plasma flow was lower per unit weight of testis. The absolute volume of each Leydig cell and the total volume in absolute terms and as a fraction of the interstitial tissue was greater in the hormone-treated than in the untreated rams, but not the volume as a fraction of the whole testis. The total number of Leydig cells was higher in the hormone-treated unheated rams than in all the other rams taken together.(ABSTRACT TRUNCATED AT 400 WORDS)

Intratesticular Control Of Steroidogenesis

Men are men because of testosterone, and the effects of this hormone are evident in virtually every organ or tissue in a normal adult man. Because testosterone is a classical endocrine hormone with effects throughout the body, many endocrinologists will have failed to realize that, in terms of its effects on fertility, the primary role of testosterone is not endocrine but paracrine, as it is the local action of testosterone on spermatogenesis which determines fertility. When looked at from this perspective it is logical to question the traditional endocrine teaching which states that testosterone secretion is controlled solely by pituitary luteinizing hormone (LH). Certainly, the levels of testosterone and LH in peripheral blood show a close relationship, but it is not the level of testosterone in peripheral blood which determines fertility. If the primary role of testosterone is within the testis, then it is not unreasonable to expect that local mechanisms may exist to regulate the intratesticular levels of this steroid. The object of this review is to examinecritically the evidence for such mechanisms, their possible nature and their physiological and clinical significance (if any). Before reviewing the data on intratesticular control of steroidogenesis it is essential to place it in perspective. To do this, three principal questions need to be answered: (I) Why might intratesticular mechanisms for local control of testosterone production be required? (2) What is the role (or roles) of testosterone within the testis? A proper understanding of how testosterone controls spermatogenesis is essential if the local regulation of testosterone production is to be evaluated from a physiological perspective. (3) What are the constraints or problems relating to studies on the intratesticular control of steroidogenesis? It is essential to understand the potential limitations of studies on this subject so that a reasoned interpretation of the results can be made. Most relevant data is derived from studies in uitro, and the relationship of such data to the situation in uivo is often difficult to establish.

The Effects of Sexual Maturation and Altered Steroid Synthesis on the Production and Route of Secretion of Inhibin-α from the Rat Testis

This study has determined the route of secretion of inhibin-alpha into blood by the rat testis during sexual maturation, and in adult animals in which Leydig cell steroidogenesis was stimulated with human CG (hCG) or suppressed with aminoglutethimide. In each rat, inhibin-alpha levels were measured in samples of testicular (TV), spermatic (SV), and peripheral (PV) venous blood plasma, and in testicular interstitial fluid (IF). The IF and TV plasma reflect inhibin-alpha secretion via the base of the Sertoli cell while that secreted via the apex of the Sertoli cell (which is resorbed from the rete testis) was determined from the difference between SV and TV levels of inhibin-alpha. During sexual maturation, inhibin-alpha levels in IF and all plasma samples declined from maximal values at 28 days of age to minimal values at 100 days of age, in contrast to testosterone levels which showed the reverse pattern. There was a major change with age in the route of secretion of inhibin-alpha from the testis into blood. In immature (28-35 days) rats, most inhibin-alpha (58-65%) leaving the testis in blood was derived from that secreted via the base of the Sertoli cell with a relatively small contribution (35-42%) from apically-secreted inhibin-alpha. However, the latter made a progressively increasing contribution between 45 and 100 days of age (adults) and in adult rats the vast majority of inhibin-alpha (95%) leaving the testis in blood was derived from apically-secreted inhibin-alpha. This change was due primarily to a progressive reduction with age in the secretion of inhibin-alpha via the base of the Sertoli cell, a change which was confirmed by inhibin bioassay. Stimulation of steroidogenesis in the adult testis with hCG significantly increased inhibin-alpha and testosterone levels in IF and all plasma samples. The concomitant administration of hCG and aminoglutethimide (to block steroidogenesis) prevented the hCG-induced increase in testosterone levels, but still led to significant increases in inhibin-alpha secretion which were comparable to those seen with the use of hCG alone. The administration of aminoglutethimide (AMG) on its own did not alter the inhibin-alpha secretion profile from that seen in controls, but it did significantly reduce the levels of testosterone in all fluids. In rats treated with hCG +/- AMG there was a small change in the route of secretion of inhibin-alpha into blood, with an increased contribution (24-37%) from inhibin-alpha secreted via the base of the Sertoli cell, when compared with controls (7-16%).(ABSTRACT TRUNCATED AT 400 WORDS)

Androgen levels in spermatic venous plasma and peripheral venous plasma of the dog during the process of sexual maturity.

Androgen levels in spermatic venous plasma and peripheral venous plasma of the dog during the process of sexual maturity.

Prorenin secretion from human testis: no evidence for secretion of active renin or angiotensinogen.

To determine if the testis secretes active renin and prorenin, we collected internal spermatic venous blood from 29 young men undergoing varicocelectomy and measured plasma prorenin and active renin together with angiotensinogen and testosterone. Prorenin was higher in internal spermatic venous plasma than in peripheral plasma (+5.3 +/- 1.2 (+/- SE) ng/mL.h [+1.21 ng/(L.s)]; P less than 0.001) as was testosterone [+344 +/- 32 ng/mL [(+1193 nmol/L; P less than 0.001], but there was no significant difference in either active renin (-0.74 +/- 0.45 ng/mL.h [-0.17 ng/(L.s)] or angiotensinogen [+12 +/- 24 ng/mL (+0.01 mumol/L)]. These results demonstrate that the testis secretes prorenin, but not active renin or angiotensinogen, into the general circulation. They support the hypothesis that extrarenal renin systems cannot process prorenin to renin.

Testicular function of scrotal testes after the cryptorchidectomy in dogs with unilateral cryptorchidism.

Cryptorchidectomy was performed in 6 adult dogs with unilateral cryptorchidism. In these dogs, semen samples were collected weekly from 2 weeks before cryptorchidectomy till 24 weeks after the operation. Peripheral venous blood samples were collected from all the dogs at intervals of 4 weeks, and spermatic venous blood samples and testicular tissue specimens were obtained at the time of the removal of cryptorchid and scrotal testes. In the scrotal testes the testosterone level of spermatic venous plasma was lower, and the number of germ cells in the seminiferous tubules was smaller than those in the testis of the normal dogs at the time of cryptorchidectomy. However, semen volume and number of sperms increased gradually, and sperm abnormality decreased after the operation. Semen quality became close to that of the normal dog 20 weeks after the operation or later. Furthermore the plasma testosterone levels and the number of germ cells increased to the same as those in the normal dog at 24 weeks after the operation. Therefore, it was concluded that in the dogs with unilateral cryptorchidism the cryptorchid testis disturbed the testicular function of the scrotal testis.

Spermatogenesis and peripheral spermatic venous plasma androgen levels in the unilateral cryptorchid dogs.

A total of 29 adult unilaterally cryptorchid dogs were examined for their spermatogenic function and plasma androgen levels. The testes, epididymides, and prostates were studied histologically. The 4-androstenedione (A), 5α-dihydrotestosterone (DHT), and testosterone (T) levels in the peripheral and spermatic venous plasma were measured by the RIA method to estimate their endocrine functions. The mean diameter of seminiferous tubules in the undescended testis was 125μm about half that in the normal testis. A few primary spermatocytes were found in the testis of about one-theird of the cryptorchid dogs. Neither spermatids nor spermatozoa were seen in any undescended testis and Leydig cells were tended to be atrophic. Primary spermatocytes and spermatids were significantly fewer in the contralateral than in the normal testis (P<0.01). The development of epididymides and prostates was demonstrated in the cryptorchid dogs. Mean spermatic venous plasma A and DHT levels were significantly higher in the cryptorchid than in normal dogs (P<0.01), in contrast to the significantly lower mean spermatic venous plasma T level (P<0.01). The peripheral venous plasma A and T levels showed the same changes as did the spermatic venous plasma androgen levels, but the DHT level was nearly equal to that in normal dogs. The spermatogenesis and T secretory function of the scrotal as well as uncescended testis in the unilateral cryptorchid dog were inferior to those in normal dogs.

Hormone levels in the reproductive system of normospermic men and patients with oligospermia and varicocele.

The endocrine milieu on which spermatogenesis and sperm maturation mainly depend was evaluated quantitatively with simultaneous measurements of FSH, LH, PRL, testosterone, estrone, estradiol (E2), and sex hormone-binding globulin concentrations in spermatic venous plasma, antecubital plasma, seminal fluid, and wash fluid from vas deferens in 16 normospermic men and 24 oligospermic patients. Anesthesia and surgical stress caused a rise of only PRL and E2 (P less than 0.001-0.01). Mean FSH, LH, and PRL levels were comparable in antecubital and spermatic venous plasma, and antecubital values were higher in oligospermic patients for FSH and LH (P less than 0.05-0.001). Mean (+/- SD) T levels were similar for normospermic and oligospermic men in spermatic venous plasma (473 +/- 75 and 439 +/- 270 ng/ml), in antecubital plasma (6.5 +/- 1.3 and 6.6 +/- 1.8), and in seminal fluid (0.3 +/- 0.1 for both). Minute quantities of testosterone were detected in pooled wash fluid (0.08 ng). For E2, similar concentration gradients from high to low levels were found in normospermic and oligospermic men (spermatic venous plasma = 926 +/- 205 pg/ml and 1090 +/- 262; antecubital plasma = 31.0 +/- 12.0 and 28.4 +/- 1.9; seminal fluid = 14.3 +/- 2.3 and 12.0 + 2.8). Estrone was also high in spermatic venous and low in antecubital plasma but higher in seminal fluid than in antecubital plasma. Sex hormone-binding globulin levels were slightly though not significantly lower in spermatic venous (23 +/- 10 nmol/liter) than in antecubital plasma (28 +/- 6), but not measurable in seminal fluid. These results define important aspects of the endocrine milieu prevailing in the male reproductive tract and demonstrate a change of the relative activity of androgens and estrogens from the testis to the seminal fluid.

Transport of free and conjugated steroids from the boar testis in lymph, venous blood and rete testis fluid.

In 12 anaesthetized boars the concentrations of oestrone sulphate and dehydroepiandrosterone sulphate (DHAS) were 15- to 35-fold higher in lymph collected from a vessel in the spermatic cord than in testicular venous blood plasma from a vein in the spermatic cord. The concentrations of testosterone, total unconjugated oestrogens and dehydroepiandrosterone (DHA) were about twofold higher in lymph. The concentrations of all steroids studied were higher in testicular venous blood plasma than in arterial blood plasma (testosterone about sixfold; total unconjugated oestrogens about fourfold; oestrone sulphate about threefold; DHA and DHAS about twofold), but the concentrations of testosterone, total unconjugated oestrogens and oestrone sulphate in rete testis fluid were comparable to those in arterial blood plasma. Lymph flow from the pig testis was about 7% of plasma flow so that about 80% of the oestrone sulphate and DHAS produced by the testis leaves the organ in the lymph; the comparable values for testosterone, total unconjugated oestrogen and DHA were about 20%. In the 90-min period following an injection of human chorionic gonadotrophin there were substantial increases in the concentration of testosterone and smaller increases in the other steroids in arterial and spermatic venous blood plasma and in testicular lymph, but not in rete testis fluid; there were also small increases in lymph flow, but no change in blood flow.

Human testis does not secrete oestrone sulphate.

The concentrations of five steroids in samples of spermatic venous blood collected from 17 men undergoing ligation of varicocoeles were compared with those in samples from the antecubital vein. There was evidence of testicular secretion of testosterone, androstenedione, oestradiol-17 beta and oestrone, since the ratios of the mean concentrations in spermatic venous plasma to those in peripheral venous plasma were 77.2, 9.1, 28.7 and 1.6 respectively. The testicular secretion of oestrone sulphate was minimal; the ratio of the mean concentrations in spermatic and peripheral plasma was 1.07. These results support the view derived from isotope dilution studies that almost all oestrone and oestrone sulphate in the circulation is derived from peripheral conversion of other precursor steroids.

Testosterone concentrations in spermatic venous blood plasma of prepubertal boys.

Testosterone concentration has been measured in spermatic and peripheral venous plasma obtained during surgery from a total of 25 prepubertal boys affected either by inguinal hernia (Group I; N = 6; age range 2-8 years) or unilateral undescended testis (Group II; N = 19; age range 5-11 years). Median spermatic venous testosterone level was 58.7 ng/dl) (range 14.0--120.8 ng/dl) in Group I and 43.2 ng/dl (range 12..2-267.5 ng/dl) in Group II; median peripheral testosterone level was 4.9 ng/dl (range 2.3-15.4 ng/dl) and 5.6 ng/dl (range 1.1-89.3 ng/dl) in Group I and II, respectively. The difference between the spermatic and peripheral level was statistically significant in both groups (P less than 0.01 in Group I and P less than 0.001 in Group II). These results indicate that the prepubertal human testis secretes testosterone, even if in a very low amount. It is also suggested that this secretion can be responsible for LH inhibition in prepubertal boys.

Measurement of 5α-androstane-3α,17β-diol in human spermatic venous plasma by mass-fragmentography

Five alpha-androstane-3α,17β-diol (3α-diol) an active metabolite of testosterone (T) was measured in the spermatic and peripheral venous blood of 6 normal males using mass-fragmentography. Using this method 3α-diol was clearly separated from the following isomers: 5α-androstane-3β,17β-diol, 5β-androstane-3α,17β-diol and 5β-androstane-3β,17β-diol. The mean concentrations (±SE) of 3α-diol in spermatic and peripheral venous blood were respectively 100 ± 38 ng/100 ml and 7.7 ± 1.9 ng/100 ml. The existence of a significant ( P < 0.01) gradient between spermatic and peripheral vein clearly demonstrates that the human testis secretes 3α-diol.

Testicular blood flow and testosterone concentrations in the spermatic venous blood in rats with experimental cryptorchidism.

Testicular blood flow and testosterone concentrations in the spermatic venous plasma were measured on unilaterally cryptorchid rats. Blood flow to the cryptorchid testis was 31.4 +/- 11.7 (SD) ml/100 g X min which was significantly higher thant that of the scrotal testis (17.7 +/- 4.4 ml/100 g X min). Stereological analysis showed a relative increase of blood vessel containing interstitial tissue in the cryptorchid testis, which was probably the main factor responsible for the relative increase of blood flow to the cryptorchid testis. The increase of interstitial tissue was greater than the increase of blood vessels and thus, the interstitium in the cryptorchid testis contained a number of vessels which was smaller than that of the interstitium in the scrotally located testis. The concentration of testosterone in the spermatic vein of the abdominal testis was 18.0 +/- 5.5 (SD) ng/ml and the corresponding value for the scrotal testis was 41.2 +/- 7.0 ng/ml. Calculations based on functional and morphological data indicate that the function of the Leydig cells in the abdominal testis was impaired. It was concluded that the outflow of testosterone from the cryptorchid testis was highly reduced.

Dihydrotestosterone and testosterone concentrations in spermatic venous blood and seminal plasma from patients affected by azoospermia due to germinal cell arrest and Sertoli cell only syndrome

Dihydrotestosterone and testosterone concentrations in spermatic venous blood and seminal plasma from patients affected by azoospermia due to germinal cell arrest and Sertoli cell only syndrome

Age-related secretion of androstenedione, testosterone and dihydrotestosterone by the human testis

Androstenedione (Δ), Testosterone (T) and Dihydrotestosterone (DHT) have been measured by radioimmunoassay in spermatic venous plasma from 38 men aged from 17 to 80 years. The concentration of T and DHT have been found significantly decreased with age, while Δ was unchanged. The presence of trouble in testicular steroidogenesis during senescence may be suspected.

Studies on the metabolism of 5alpha-androst-16-en-3-one in boar tests in vivo.

1. [5alpha-(3)H]5alpha-Androst-16-en-3-one (5alpha-androstenone) was infused at a constant rate for 180min into the spermatic artery of a sexually mature boar. Samples of spermatic-venous blood were collected at 1min intervals for the first 10min of the infusion and thereafter at 15min intervals for the first hour, then at 64, 125, 155 and 172min. After infusion, the testis was removed and immediately cooled to -196 degrees C. 2. From both the testicular tissue and the spermatic-venous plasma, endogenous and (3)H-labelled androst-16-enes were isolated, characterized and quantitatively determined and their specific radioactivity was calculated. 3. The specific radioactivities of 5alpha-androstenore, 5alpha-androst-16-en-3alpha-ol and 5alpha-androst-16-en-3beta-ol (an-alpha and an-beta) in testicular tissue were different from those in the spermatic-venous plasma, suggesting that these compounds may be present in more than one compartment of the testis and differentially secreted into the spermatic-venous blood. 4. The ratios of the specific radioactivities of an-alpha and an-beta to their respective sulphate conjugates in the testicular tissue were less than the ratios of the same compounds in the spermatic-venous plasma. 5. The patterns of secretion of these labelled compounds in the spermatic-venous blood during the period of infusion were demonstrated. 6. The urine that accumulated during the infusion was analysed and found to contain (3)H-labelled an-beta, conjugated as both glucuronide and sulphate, the specific radioactivities of which were determined. Little or no androst-16-enes occurred as free steroids. 7. The presence of an-beta glucuronide in the urine is discussed.

Familial male pseudohermaphroditism without gynecomastia due to deficient testicular 17-ketosteroid reductase activity.

Abstract To evaluate possible 17-ketosteroid reductase deficiency, we studied two sisters with primary amenorrhea, hirsutism, clitoral enlargement and a 46,XY karyotype, who lacked breast development. Plasma luteinizing hormone, follicle-stimulating hormone and urinary 17-ketosteroids were elevated in both subjects. Plasma Δ4-androstenedione was seven to nine times greater than normal, whereas plasma testosterone was low or in the low-normal male range. Spermatic venous plasma of Case 2 contained increased amounts of Δ4-androstenedione and estrone and subnormal amounts of testosterone and estradiol, findings consistent with testicular 17-ketosteroid reductase deficiency. In vitro incubation of testicular tissue of Case 2 confirmed a partial defect in testicular 17-ketosteroid reductase activity and documented increased 3β-hydroxysteroid dehydrogenase activity. Failure of breast development was probably due to lower estrogen levels than in previously reported cases. We conclude that testicular 17-ketostero...

Secretion of unconjugated androgens and estrogens by the normal and abnormal human testis before and after human chorionic gonadotropin.

The secretion of androgens and estrogens by normal and abnormal testes was compared by determining the concentrations of dehydroepiandrosterone (DHEA), androstenedione (Delta(4)A), testosterone (T), estrone (E(1)), and 17beta-estradiol (E(2)) in peripheral and spermatic venous plasma samples from 14 normal men and 5 men with unilateral testicular atrophy. Four normal men and one patient with unilateral atrophy of the testis were given human chorionic gonadotropin (HCG) before surgery. Plasma estrogens were determined by radioimmunoassay; plasma androgens were measured by the double-isotope dilution derivative technique. Peripheral concentrations of these steroids before and after HCG were similar in both the normal men and the patients with unilateral testicular atrophy. In normal men, the mean +/-SE spermatic venous concentrations were DHEA, 73.1+/-11.7 ng/ml; Delta(4)A, 30.7+/-7.9 ng/ml; T, 751+/-114 ng/ml; E(1), 306+/-55 pg/ml; and E(2), 1298+/-216 pg/ml. Three of four subjects with unilateral testicular atrophy had greatly diminished spermatic venous levels of androgens and estrogens. HCG treatment increased the testicular secretion of DHEA and T fivefold, Delta(4)A threefold, E(1) sixfold, and E(2) eightfold in normal men. In the single subject with an atrophic testis who received HCG, the spermatic venous concentrations of androgens and estrogens were much less than in normal men similarly treated. We conclude that: (a) E(1) is secreted by the human testis, but testicular secretion of E(1) accounts for less than 5% of E(1) production in normal men; (b) HCG stimulation produces increases in spermatic venous estrogens equal to or greater than the changes in androgens, including testosterone; and (c) strikingly decreased secretion of androgen and estrogen by unilateral atrophic human tests cannot be appreciated by analyses of peripheral steroid concentrations.

Studies on the biosynthesis in vivo and excretion of 16-unsaturated C 19 steroids in the boar.

1. In one experiment [7alpha-(3)H]pregnenolone was infused continuously for 12min into the left spermatic artery of a sexually mature boar and blood was collected during this period by continuous drainage from the spermatic vein. After infusion, the testis was removed and immediately cooled to -196 degrees C. 2. From both the testicular tissue and the spermatic venous plasma, (3)H-labelled 16-unsaturated C(19) steroids were isolated and characterized and their radiochemical purity was established. 5alpha-Androst-16-en-3alpha- and 3beta-ol occurred mainly as sulphate conjugates and to a lesser extent as free steroids. Only traces of these alcohols occurred as glucosiduronate conjugates. 5alpha-Androst-16-en-3-one was found in the free (ether-extractable) fraction. 3. The isotope concentration of each of the (3)H-labelled 16-unsaturated C(19) steroids in testicular tissue was different from that in spermatic venous plasma. 4. The ratios of tritiated 5alpha-androst-16-en-3alpha- and 3beta-ol (free steroids) to their respective sulphate conjugates in the testicular tissue were less than the ratios of the same compounds in the spermatic venous plasma. The possibility that the sulphates are partially hydrolysed by testicular sulphatases before secretion is discussed. 5. In a second experiment, a continuous close-arterial infusion of [7alpha-(3)H]pregnenolone into the left testis was performed over a 200min period and all the urine that accumulated during the infusion was collected for analysis. 6. No (3)H-labelled 16-unsaturated C(19) steroids were detected in the urine as free steroids. Only a trace of 5alpha-androst-16-en-3alpha-ol was detected conjugated as glucosiduronate, whereas the corresponding 3beta-alcohol occurred mainly as glucosiduronate and to a lesser extent as sulphate. 7. The absence of 5alpha-androst-16-en-3beta-ol glucosiduronate in the spermatic venous blood and its presence in considerable amount in the urine may be attributed to hepatic glucuronyl transferase activity.