A comparison of Leydig cell function after unilateral and bilateral cryptorchidism and efferent-duct-ligation

Surgical induction of cryptorchidism or ligation of the efferent ducts disrupts spermatogenesis. The response of Leydig cells to disrupted gametogenesis was studied in vitro in tissue and collagenase dispersed Leydig cells obtained from the testes of rats that were made unilaterally or bilaterally cryptorchid or had been efferent-duct-ligated. Four wks after surgery, androgen secretion per mg of tissue or per Leydig cell in response to maximal luteinizing hormone (LH) stimulation was greater in tissue from damaged than from sham-operated testes. It was concluded that disruption of spermatogenesis resulted in Leydig cells that were hyperresponsive to LH stimulation in vitro. Unilateral lesions produced different responsiveness of Leydig cells from the testes ipsilateral and contralateral to the lesion, supporting the hypothesis that intragonadal modulation of Leydig cells function occurs when the function of seminiferous tubules is impaired. Stimulated androgen production of Leydig cells from the contralateral nonligated testis did not differ from that of the sham-operated controls. With unilateral cryptorchidism, which is accompanied by an increase in the temperature of the operated testis, Leydig cells from the scrotal testis were also hyperresponsive compared to those from sham-operated controls. This suggests a possible intergonadal influence of aspermatogenesis caused by cryptorchidism.     

Effect of uni- and bilateral cryptorchidism on testicular inhibin and testosterone secretion in rats

The effect of uni- and bilateral cryptorchidism on testicular inhibin and testosterone secretion and their relationships to gonadotropins were studied in rats. Mature Wistar male rats weighing approximately 300 g were made either uni- or bilaterally cryptorchid. Testicular inhibin and testosterone content and plasma levels of LH and FSH were examined 2 weeks later. A similar remarkable decrease in testicular inhibin content was found in uni- and bilaterally cryptorchid testes. On the other hand, the testicular testosterone content was significantly decreased only in unilaterally cryptorchid testis with an inverse increase in the contralateral testis. Plasma testosterone levels were normal and plasma LH and FSH increased significantly in both of the cryptorchid groups. These results showed that cryptorchidism impairs both Sertoli and Leydig cell functions. While testosterone production was compensated by increased LH for 2 weeks, neither inhibin secretion nor storage changed in cryptorchid or contralateral testes during the same period.     

Effects of the induction of experimental cryptorchidism and subsequent orchidopexy on testicular function in immature rats

Cryptorchidism surgically induced in 14-day-old rats, was allowed to persist until 35 days when one group was killed to assess testicular function. In a second group the cryptorchid testis was returned to the scrotum surgically (orchidopexy) and subsequently killed at 130 days. A third group remained persistently cryptorchid to 130 days, while in a fourth group two sham operations were performed at 14 and 35 days. At 35 days, cryptorchidism resulted in a significant decline in testis weight due to suppressed spermatogenesis. Sertoli cell function as measured by seminiferous tubule fluid (TF) production after unilateral efferent duct ligation and androgen-binding protein (ABP) production was significantly depressed in the cryptorchid group. Serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were significantly elevated with cryptorchidism but serum testosterone levels were unchanged. Although morphometric measurements showed no change in Leydig cells cross-sectioned area, in vitro human chorionic gonadotropin (hCG)-stimulated testosterone production was significantly increased in the cryptorchid group at higher hCG doses. Similar changes were found in cryptorchid testes at 130 days except that Leydig cell cross-sectional area was now significantly increased. Orchidopexy at 35 days restored spermatogenesis and fertility during test mating was not impaired. TF production, ABP accumulation and serum FSH levels returned to normal following orchidopexy.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of prenatal treatment with busulfan on in vitro androgen production by testes from rats of various ages

Treatment of rats with busulfan in utero severely depletes the germ cell population of the seminiferous tubules. These studies have examined the in vitro capacity of testicular tissue and Leydig cells from such testes to secrete androgens. Leydig cells were identified by staining for 3 beta-hydroxy steroid dehydrogenase. Rats were studied at several ages to identify any developmental changes in the androgen-secreting capacity of control and treated gonads. At 30 days of age, no effect of treatment on serum androgen was found. At 60 and 90 days of age, treatment caused decreased androgen and increased LH content of the serum. At 12, 30, 60, and 90 days of age, the amount of androgen secreted per milligram of testicular tissue in response to LH was higher in busulfan-treated rats. Leydig cells from 60- and 90-day-old rats which had received busulfan were also hyperresponsive to LH. It was concluded that Leydig cells from testes essentially devoid of germ cells were hyperresponsive to LH. Serum androgen levels were decreased yet androgen production per Leydig cell was increased. A possible explanation of this apparent paradox is that busulfan treatment resulted in decreased numbers of Leydig cells in the gonads.     

Temporal changes in rat Leydig cell function after the induction of bilateral cryptorchidism

Adult rats were made bilaterally cryptorchid and studied at intervals of 3, 7, 14 or 21 days to study temporal changes in Leydig cell function. Serum FSH and LH levels were measured and the cross-sectional area of the Leydig cells assessed by morphometry. The function of the Leydig cells was judged by the binding of 125I-labelled hCG to testicular tissue in vitro and the testosterone response of the testis to hCG stimulation in vitro. By 3 days after cryptorchidism, the binding of labelled hCG to testicular tissue was significantly decreased compared to that of controls, but the testes were able to respond to hCG stimulation in vitro. At 7, 14 and 21 days after cryptorchidism, an enhanced testosterone response was observed and the size of the Leydig cells was significantly greater than that of the controls, which indicated increased secretory activity by the cryptorchid testis. Although serum FSH levels were significantly elevated after 3 days of cryptorchidism, serum LH levels did not rise until 7 days, thereby suggesting that the loss of receptors is unlikely to result from down-regulation by LH. The reduced testosterone response of the cryptorchid testis in vivo to low doses of hCG and the enhanced response at high doses are probably related to the reduced blood flow to the cryptorchid testis and the decreased sensitivity of the Leydig cells induced by LH/hCG receptor loss.     

Testosterone restores testicular inhibin content in cryptorchid rats

The effects of testosterone administration on testicular inhibin content and histology were studied in bilaterally cryptorchid rats, in which a marked decrease in testicular inhibin content had been observed. Mature male Wistar rats weighing approximately 300 g were made bilaterally cryptorchid by placing the testes in the abdominal cavity. Testosterone in oil, 0.1, 1.0 or 10 mg, was given i.m. each week. Testicular inhibin and testosterone content, histology and plasma LH, FSH and testosterone were studied 2 weeks later. Abnormally decreased testicular inhibin in cryptorchidism was restored toward normal by testosterone in a dose dependent manner in 2 weeks after surgery. Sertoli cell structure also recovered toward normal with increasing amount of testosterone. Decreased testicular testosterone content and Leydig cell atrophy were observed with suppressed plasma LH and FSH after testosterone. These results showed that the increased plasma concentration of testosterone had a stimulatory effect on the Sertoli cell function in cryptorchidism, in which compensated Leydig cell failure was demonstrated.     

Disruption of spermatogenesis is associated with decreased concentration of immunoreactive arginine vasopressin in testicular fluid

We have previously shown that testicular fluid contains factors that can inhibit luteinizing hormone (LH)-stimulated androgen production by Leydig cells, and others have reported the presence of immunoreactive vasopressin (iAVP) in the testes as well as in vitro inhibition by vasopressin of Leydig cell-androgen production. In the current report, we have used an established radioimmunoassay (RIA) to measure the concentration of iAVP in testicular fluid and have related changes in iAVP concentration to disruption of the seminiferous tubules. Spermatogenesis was disrupted in adult rats by surgically establishing bilateral cryptorchidism. The concentration of iAVP decreased progressively from 349 +/- 52 to 61 +/- 5 pg/ml during 4 wk. When cryptorchidism was unilaterally established, the concentration of iAVP in fluid from that testis decreased to 116 +/- 19 pg/ml while the concentration of iAVP in the contralateral scrotal testis remained unaffected. Unilateral ligation of the ductuli efferentes also caused an equivalent unilateral decrease in iAVP to 110 +/- 15 pg/ml. The osmotic pressure of the testicular fluid was not altered by disruption of gametogenesis, and the extracellular "albumin space" was not increased. Therefore, the decrease in concentration of iAVP was probably not due to dilution with increased amounts of interstitial fluid. We conclude that the disruption of spermatogenesis is associated with a decrease in the concentration of iAVP in testicular fluid and suggest that AVP or a similar peptide may be involved in the intratesticular mechanisms associated with increased production of androgen by Leydig cells after disruption of spermatogenesis.     

Testicular function and Leydig cell ultrastructure in long-term bilaterally cryptorchid rams

This study was conducted to investigate the effects of bilateral cryptorchidism induced in adult rams on testicular function and Leydig cell ultrastructure. The results indicated that long-term bilateral cryptorchidism resulted in decreased testicular size, degeneration of seminiferous tubules, elevated serum LH levels, maintenance of normal testosterone concentrations in peripheral and spermatic vein serum, impairment of the magnitude and duration of androgen response to exogenous luteinizing hormone (LH), a 13-fold reduction in total number of Leydig cells/paired testes, and a 3-fold hypertrophy in the average size of remaining Leydig cells. Based on quantitative morphometry, the hypertrophied Leydig cells exhibited significant increases in the volume of intracellular organelles, including the cell nucleus, mitochondria, smooth and rough endoplasmic reticulum, lysosome-like bodies and lipid vesicles. Quantitatively, the hypertrophy alone was not enough to offset the loss in number of Leydig cells and was insufficient to explain the maintenance of normal levels of testosterone in jugular and spermatic venous blood. The additional mechanisms responsible for production of normal serum testosterone levels in the cryptorchid ram remain to be elucidated.     

Androgen secretion and characteristics of testicular HCG binding in cryptorchid rats

Response of the cryptorchid testis to gonadotrophic stimulation was assessed by comparison of the androgen production capability in vivo and in vitro with that of the normal scrotal testis. Serum androgen concentrations in cryptorchid rats were similar to those in normal rats, and the incremental increase 60 min after 50 i.u. hCG (i.v.) was about 7-fold for both groups. Basal and hCG-stimulated androgen production in vitro was higher for abdominal testes (557 and 3286 ng/pair) than for scrotal tests (157 and 504 ng/pair). Specific binding of hCG by testicular homogenates was slightly higher (P < 0.05) for cryptorchid testes when expressed per unit weight, but Scatchard analysis indicated that although hCG binding affinities did not differ (Ka = 2 x 10(10) M-1), hCG binding capacity of cryptorchid testes was only 75 ng, compared to 219 ng for scrotal testes. These data indicate that a discrepancy exists between androgen production in vivo and in vitro by cryptorchid testes and that normal serum androgen concentrations are maintained in the presence of decreased numbers of testicular LH/hCG receptors.     

Changes of testicular cholesteryl ester hydrolase activity in experimentally cryptorchid rats

A simple and reliable method was developed to determine the neutral cholesteryl ester hydrolase (CEH) activity in rat testes, using cholesteryl-[1-14C]-oleate as substrate. The activity was due to a soluble enzyme present in the cytoplasm of predominantly Sertoli cells, which could be shown after depleting the testes of Leydig cells with ethane dimethyl sulphonate. This treatment also revealed that the loss of CEH activity in abdominal testes of experimentally cryptorchid rats takes place in the Sertoli cells. In prepubertal rats made unilaterally cryptorchid at birth, the CEH activity was significantly higher in the abdominal than in the scrotal testes at 16 days of age. This is earlier than any previously described biochemical change and coincides with, or may even precede, the earliest morphological changes which are accumulation of lipid droplets in the Sertoli cells. The testicular CEH activity then decreased to 30 days of age in the abdominal testes, whereas the activity increased in the contralateral, scrotal testes. When adult rats were made unilaterally cryptorchid for 24 h, the CEH activity decreased rapidly in the abdominal testes. These results suggest that a derangement in cholesteryl ester metabolism is an early event in the pathogenesis of testicular degeneration in cryptorchidism.     

Testosterone, androstenedione, progesterone and 17 alpha-hydroxyprogesterone in plasma and testes of immature rats under basal conditions and after hCG stimulation. Effect of bilateral cryptorchidism

Rats were made bilaterally cryptorchid at 21 days of age; sham-operated rats were used as controls. At 35 days, the animals were injected i.m. with saline or with 10 IU hCG. Progesterone, 17-hydroxyprogesterone, androstenedione and testosterone were measured in both testes and plasma under basal conditions and 2, 4, 8, 12, 24 and 72 h respectively after injection. The plasma levels and intratesticular contents of the steroids were generally lower in cryptorchid rats. The patterns of the steroid response to hCG were similar in both groups: in the testes and in the plasma, they increased acutely following hCG injection (except testicular androstenedione), then, after 72 h, returned to normal values in the plasma but remained higher than the basal values in the testes. These results suggest that there are no gross abnormalities in the testicular steroidogenic pathways and that the mechanism of action of hCG on the Leydig cells is unaltered in bilaterally cryptorchid immature rats.     

The effects of cryptorchidism on the regulation of steroidogenesis and gap junctional communication in equine testes

INTRODUCTION: Evidence collected over the years has demonstrated that cryptorchidism is associated with a defect in spermatogenesis and, as a consequence, with either reduced fertility or infertility. However, the effect of cryptorchidism on Leydig cell function is less clear. The aim of our study therefore was to investigate the regulation of steroid hormone biosynthesis and, additionally, intercellular communication in the cryptorchid equine testes. MATERIAL AND METHODS: Testes of mature bilaterally cryptorchid horse and healthy stallions were used for this study. The expression of luteinising hormone receptor (LHR), 3beta-hydroxysteroid dehydrogenase (3beta-HSD), aromatase and connexin43 (Cx43) was detected by means of immunohistochemistry. Testosterone and oestradiol levels were measured in testicular homogenates using appropriate radioimmunoassays. RESULTS: In the testes of both normal and cryptorchid stallions, immunostaining for LHR, 3beta-HSD and aromatase was confined to the Leydig cells. In the cryptorchid horse, the intensity of the staining for LHR and 3beta-HSD was weaker, whereas the staining for aromatase was clearly stronger than that of the normal stallion. Radioimmunological analysis revealed disturbance of the androgen-oestrogen balance in the cryptorchid testes. Additionally, in both the seminiferous tubules and interstitial tissue of the cryptorchid a clear reduction of the Cx43 signal was observed. CONCLUSIONS: Decreased expression of LHR and 3beta-HSD and increased expression of aromatase in the cryptorchid testes suggest that hormonal imbalance was caused both by reduced testosterone synthesis and by increased androgen aromatisation. Impaired expression of Cx43 in the seminiferous tubules as well as in the interstitial tissue of the cryptorchid horse indicates that cryptorchidism affects intercellular communication in the testes.     

Environmental effects on hormonal regulation of testicular descent

Regulation of testicular descent is hormonally regulated, but the reasons for maldescent remain unknown in most cases. The main regulatory hormones are Leydig cell-derived testosterone and insulin-like factor 3 (INSL3). Luteinizing hormone (LH) stimulates the secretion of these hormones, but the secretory responses to LH are different: INSL3 secretion increases slowly and may reflect the LH dependent differentiated status of Leydig cells, whereas testosterone response to LH is immediate. Testosterone contributes to the involution of the suspensory ligament and to the inguinoscrotal phase of the descent, while INSL3 acts mainly in transabdominal descent by stimulating the growth of the gubernaculum. INSL3 acts through a G-protein coupled receptor LGR8. In the absence of either INSL3 or LGR8 mice remain cryptorchid. In humans only few INSL3 mutations have been described, whereas LGR8 mutations may cause some cases of undescended testis. Similarly, androgen insensitivity or androgen deficiency can cause cryptorchidism. Estrogens have been shown to down regulate INSL3 and thereby cause maldescent. Thus, a reduced androgen–estrogen ratio may disturb testicular descent. Environmental effects changing the ratio can thereby influence cryptorchidism rate. Estrogens and anti-androgens cause cryptorchidism in experimental animals. In our cohort study we found higher LH/testosterone ratios in 3-month-old cryptorchid boys than in normal control boys, suggesting that cryptorchid testes are not cabable of normal hormone secretion without increased gonadotropin drive. This may be either the cause or consequence of cryptorchidism. Some phthalates act as anti-androgens and cause cryptorchidism in rodents. In our human material we found an association of a high phthalate exposure with a high LH/testosterone ratio. We hypothesize that an exposure to a mixture of chemicals with anti-androgenic or estrogenic properties (either their own activity or their effect on androgen–estrogen ratio) may be involved in cryptorchidism.     

Differences in aromatase activity between Leydig cells from the scrotal and abdominal testis in the naturally unilateral-cryptorchid boar

In an earlier study, estrogen production was much lower in Leydig cells from the abdominal than from the scrotal testis in naturally occurring unilateral cryptorchidism in the boar. A more direct assessment of aromatase activity was made in thirty-two mature male pigs to examine this observation further, using nonradioactive androstenedione (delta 4A 1.0 x 10(-6) M - 1.5 x 10(-5) M) and [1 beta, 2 beta-3H] delta 4A as substrates. Purified Leydig cells were prepared from normal boars and from unilaterally and bilaterally cryptorchid animals. Combined estrone sulfate (E1S) and estrone (E1) formation from delta 4A were measured by radioimmunoassay. Little or no estrogen secretion was seen with cells from the abdominal testis in unilaterally cryptorchid boars (n = 7), and E1S formation from delta 4A was 6- to 14-fold higher for scrotal cells (n = 6). Aromatase activity as reflected in percent conversion of substrate to [3H]-labeled water was clearly lower in cells from the abdominal testis (1.10 +/- 0.08 and 11.22 +/- 0.7%, respectively, p less than 0.01, n = 6). No marked reduction was noted for unilaterally cryptorchid boars with an inguinally located testis (10.18 +/- 0.27 and 13.09 +/- 0.58% for inguinal and scrotal testes, respectively, n = 3). Concentrations of E1S in testicular arterial and venous blood (n = 9) gave additional evidence of lower estrogen production by the undescended testis of the cryptorchid boar. It was concluded that lower aromatase activity is present in Leydig cells of the abdominal testis.     

Sertoli cell development and function in an animal model of testicular dysgenesis syndrome

Pregnancy exposure to di(n-butyl) phthalate (DBP) in rats induces a testicular dysgenesislike syndrome (TDS) in male offspring. Earlier studies suggested altered Sertoli cell development/maturation may result, especially in testes that become cryptorchid. This study quantitatively assessed Sertoli cell numerical and functional development in DBP-exposed rats and compared (unilaterally) cryptorchid and scrotal testes. Pregnant rats were gavaged with 500 mg/kg/day DBP or corn oil from embryonic (E) Days 13.5 to 21.5. Male offspring were sampled on E21.5 or Postnatal Day 6, 10, 15, 25, or 90. Sertoli cell number in DBP-exposed males was reduced by approximately 50% at E21.5 but recovered to normal by Days 25-90, accompanied by significant changes in plasma inhibin B and testosterone levels. Sertoli cell maturational development in DBP-exposed males, assessed using five protein markers (anti-müllerian hormone, cytokeratin, androgen receptor, CDKN1B, and Nestin), was largely normal, with some evidence of delayed maturation. However, in adulthood, Sertoli cells (SC) in areas lacking germ cells (Sertoli cell-only [SCO] tubules) often exhibited immature features, especially in cryptorchid testes. Sertoli cells in DBP-exposed animals supported fewer germ cells during puberty, but this normalized in scrotal testes by adulthood. Scrotal and especially cryptorchid testes from DBP-exposed animals exhibited abnormalities (SCO tubules, focal dysgenetic areas) at all postnatal ages. Cryptorchid testes from DBP-exposed animals exhibited more Sertoli cell abnormalities at Day 25 compared with scrotal testes, perhaps indicating more severe underlying Sertoli cell malfunction in these testes. Our findings support the concept of altered Sertoli cell development in TDS, especially in cryptorchid testes, but show that maturational defects in Sertoli cells in adulthood most commonly reflect secondary dedifferentiation in absence of germ cells.     

Impaired gonadotrophin uptake in vivo by the cryptorchid rat testis

The specific testicular uptake in vivo of 125I-labelled hCG was compared in control adult rats and adult rats made bilaterally cryptorchid 5 weeks previously. Although a similar temporal pattern of uptake was observed in both groups, uptake of hCG by cryptorchid testes was reduced at all times after injection by up to 70%. The possible causes of this impairment were investigated. It could not be accounted for by differences in the rate of absorption or clearance of 125I-labelled hCG in the two groups. Therefore, because hCG-induced increase in the permeability of testicular capillaries is a crucial factor in determining hCG uptake by the testis, this change was compared in control and cryptorchid testes. Although hCG induced a characteristic increase in testicular capillary wall permeability in both groups, this change was temporally delayed in cryptorchid testes, and occurred after hCG values in the blood had fallen. Even when hCG had crossed the capillary wall into testicular interstitial fluid, its uptake into the testicular tissue was significantly lower in cryptorchid than in control testes. These changes probably account for the impairment of gonadotrophin uptake by the cryptorchid testis and have important implications with respect to the aetiology of Leydig cell changes in cryptorchidism.     

Suprainguinal ectopic scrota of TS inbred rats

A new rat line (TS inbred rats) showing uni- or bilateral ectopic scrota in about 70% of the males was established. Ectopic scrota were elongated pouches of the thin muscle layer under the suprainguinal body skin, in which hypoplastic testes and epididymides were seen. Genetic analysis revealed that the ectopic scrotum was controlled by multiple genes. Groups of 5 normal, uni- and bilaterally affected rats were killed at 25 weeks of age. Histologically, ectopic testes of uni- and bilaterally affected rats showed arrest of spermatogenesis at the primary spermatocyte stage. Contralateral testes of unilaterally affected rats were normally descended and showed normal spermatogenesis. No abnormality was seen in the urinary system. Plasma concentrations of FSH were significantly elevated in bilaterally affected rats but plasma concentrations of testosterone and LH were unchanged in uni- and bilaterally affected rats. Pituitary contents of LH and FSH were significantly elevated in bilaterally affected rats. The endocrinological status of TS inbred rats was therefore similar to that of experimentally induced cryptorchid rats.     

Developmental change in the ability of estradiol to suppress testosterone secretion by the testis of the rat

An intratesticular site of action has been proposed for the ability of estradiol (E2) to suppress testosterone secretion. Because testicular testosterone and E2 secretion as well as E2 receptors change during development, a physiologic role for E2 is possible. The present experiments compared the testes from 12-day-old and adult rats for the capacity of in vivo estradiol treatment to change in vitro androgen secretion in response to luteinizing hormone (LH) and dibutyryl cyclic AMP (Bt2cAMP). After 5 days in vivo treatment, in vitro responsiveness was estimated by radioimmunoassay (RIA) measurement of androgen secretion elicited by various doses of NIAMDD-LH-24 or 1.0 mM Bt2cAMP. Five days of E2 alone (500 ng/g BW s.c. once daily) markedly inhibited basal, LH-stimulated and Bt2cAMP-stimulated androgen production at both ages. Similar treatment of infant rats with LH (100 ng NIAMDD-LH-24/g BW) caused an increase in basal and LH-stimulated androgen secretion in vitro, but had no effect on the response to Bt2cAMP. The same pretreatment of adults with LH had no effect on basal, but inhibited LH- or Bt2cAMP-stimulated androgen secretion. Combined treatment of infants with E2 and LH for 5 days had no effect on basal or maximally stimulated androgen production; the in vitro response to submaximal stimulation with LH was significantly inhibited. Combined E2/LH treatment of adults significantly decreased the basal production of androgens and the response to LH or Bt2cAMP. These results suggest a major difference between the response to E2 of the Leydig cells from the rats of the two ages tested.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of restraint stress on plasma LH and testosterone concentrations, Leydig cell LH/hCG receptors, and in vitro testicular steroidogenesis in adult rats

We examined the effect of restraint stress (3 hr) on plasma LH and testosterone levels, on the Leydig cell LH/hCG receptor, and on the activity of enzymes in the testicular steroidogenic pathway of the adult rat. Restraint stress caused a 47% reduction in plasma testosterone concentrations, but had no effect on plasma LH levels. The binding capacity and affinity of Leydig cell LH/hCG receptors were not affected by restraint. Stress did not affect the testicular activity of 20,22 desmolase or 3 beta-hydroxysteroid dehydrogenase, but testicular interstitial cells of stressed rats incubated in vitro with progesterone as a substrate produced more 17 alpha-hydroxyprogesterone but less testosterone than control cells, and when incubated with 17 alpha-hydroxypregnenolone, produced 39% less androstenedione and 40% less testosterone than control cells. These results suggest that restraint stress inhibited 17,20 desmolase but not 17 alpha-hydroxylase activity. When the delta 4 pathway was blocked with cyanoketone (3 beta-HSD inhibitor), stress did not alter the production of pregnenolone or 17 alpha-hydroxypregnenolone, but the production of dehydroepiandrosterone by cells from stressed rats was subnormal, suggesting again a reduction of 17,20 desmolase activity. The data suggest that a major site of the inhibitory action of restraint stress on testicular steroidogenesis is the 17,20 desmolase step. The disruption of androgen production by restraint appears to be LH independent since stress did not affect plasma LH levels, the binding capacity or affinity of LH/hCG receptors, or the activity of 20,22 desmolase.     

Regulation of gonadal androgen secretion

The various mechanisms regulating testicular and ovarian androgen secretion are reviewed. Testicular androgen secretion is controlled by luteinizing hormone (LH) and follicle stimulating hormone (FSH), which influence the Leydig cell response to the LH. The contribution of prolactin, growth hormone and thyroid hormones to the Leydig cell function is discussed. The ovarian androgen secretion is regulated in a very similar fashion as the Leydig cell of testis. Prolactin, however, has an inhibitory effect on androgen secretion in the ovary. The intratesticular action of androgens is linked to spermatogenesis. Sertoli cells, by producing the androgen-binding protein, contribute to the intratubular androgen concentration. Inhibin production of the Sertoli cell is stimulated by androgens. In the ovary, androgens produced by the theca interna are used as precursors for the aromatization of estradiol, which stimulates together with FSH the mitosis of granulosa cells. The feedback control of androgen secretion is complicated, as the direct feedback mechanisms are joined by indirect feedback regulations like the peptide inhibin, which can be stimulated by androgens. Intragonadal mechanisms regulating androgen production are the cybernins for testicles and ovaries. In the testicle, estrogens from the Sertoli cells regulate the Leydig cell testosterone biosynthesis. In the ovary, nonaromatizable androgens are potent inhibitors of the aromatization activity in the granulosa cell. A peptide with a FSH receptor binding inhibiting activity is found in male and female gonads. Finally, LH-RH-like peptides have been found in the testicle, which are capable of inhibiting steroidogenesis. These gonadocrinins are similarly produced in granulosa cells of the ovary.