Alterations in spermatogenic activity and hormonal status in a seasonally breeding rat,Rattus fuscipes

The changes in the levels of serum FSH, LH, and testosterone have been studied during the seasonal reproductive cycle in males of the species Rattus fuscipes. In males captured in winter the seminiferous tubules were small, spermatogenesis was arrested at the primary spermatocyte stage, and the Sertoli cells contained increased numbers of lipid inclusions. The Leydig cells were atrophic and contained large crystalloids. The aspermatic state was accompanied by low levels of serum FSH, LH, and androgen. Reactivation of spermatogenesis occurred in spring and was accompanied by a rise in the levels of FSH, LH, and androgen. These hormonal changes were associated with a depletion of lipid inclusions from the Sertoli cells which paralleled the activation of spermatogenesis. The rising androgen levels were accompanied by the enlargement of Leydig cells and the disappearance of the crystalloids. In summer the fully active testes were associated with further increments of serum FSH and androgen levels above those seen during spring. It is concluded that the environmental cues controlling the seasonal reproductive cycle exert their influence on the testis through changes in gonadotrophin secretion by the pituitary gland.     

Effect of intratesticular administration of gonadotropins on testicular and plasma androgen concentration in the lizard, Uromastix hardwicki

An acute effect of intratesticular injections of varying doses of ovine FSH (NIH-FSH-S12), ovine LH (NIH-LH-S20), and a lizard hypophyseal extract was observed on testicular and plasma androgen concentrations in Uromastix hardwicki. FSH and LH were used in a dose range of 0.25–4.00 ng and the hypophyseal extract was administered at concentrations representing 10–160 μg of fresh pituitary tissue obtained from adult male Uromastix. The test material was injected directly into one testis while the contralateral testis was likewise treated with an equal volume of saline. The control lizards received intratesticular injections of saline on both sides. Testicular and plasma androgen concentrations were measured 3 hr following the injections, using a specific RIA for testosterone. A significant increase in androgen concentration both in the testis and the plasma was obtained with 0.25 ng of FSH and 4.00 ng of LH. Both FSH and LH induced a significant rise in plasma androgen at 1.00 ng, but the increase was markedly greater in the FSH treated lizards. The homologous hypophyseal extract was shown to be active at the minimum dose level used (10 μg). The testosterone content of the uninjected testis in treated lizards was not significantly different from that of the control lizards. It is concluded that the intratesticular route of administration can be used as a sensitive and rapid method for studying in vivo responsiveness of the testis to mammalian and nonmammalian gonadotropins.     

The relative roles of follicle-stimulating hormone and luteinizing hormone in maintaining spermatogonial maturation and spermiation in normal men

CONTEXT: Male hormonal contraception via gonadotropin and intratesticular androgen withdrawal disrupts spermatogenesis at two principal sites: 1) spermatogonial maturation, and 2) spermiation. OBJECTIVE: The objective of this study was to explore the relative dependence of each stage of germ cell development on FSH and LH/intratesticular androgen action. DESIGN, SETTING, AND PARTICIPANTS: Eighteen men enrolled in this prospective, randomized 14-wk study at Prince Henry's Institute. INTERVENTIONS: Subjects (n = 6/group) were assigned to 6 wk of 1) testosterone (T) implant (4 x 200 mg sc once)+depot medroxy progesterone acetate (DMPA; 150 mg im once); 2) T implant+DMPA+FSH (300 IU sc twice weekly); and 3) T implant+DMPA+human chorionic gonadotropin (hCG; 1000 IU sc twice weekly as an LH substitute). Men then underwent a vasectomy and testicular biopsy with previously reported control data used for comparison. MAIN OUTCOME MEASURES: Germ cell number (assessed by the optical disector stereological approach) and intratesticular androgen levels were determined. RESULTS: T+DMPA alone significantly suppressed type B spermatogonia, preleptotene through to pachytene spermatocytes, and round spermatids from control (P < 0.05). All germ cell subtypes were maintained at control levels by either FSH or LH activity, except pachytene spermatocytes, which were found to be lower in the hCG vs. FSH (P < 0.01) and control groups (P < 0.05). CONCLUSIONS: FSH and LH maintained spermatogenesis independently in this gonadotropin-suppressed model. Compared with LH, FSH showed better maintenance of pachytene spermatocyte number, whereas improved conversion to round spermatids was suggested with hCG treatment. Future contraceptive treatment strategies must consider independent regulation of spermatogenesis by both FSH and LH/intratesticular androgens for maximum efficacy.     

SPECIFIC CONTROL OF FOLLICLE STMULATING HORMONE IN THE MALE: POSTULATED SITE OF ACTION OF INHIBIN

Serum luteinizing and follicle stimulating hormone concentrations were related to gonadal function, as reflected by sperm count and serum testosterone concentrations, in a group of men studied over 10 years after surgical correction of bilateral cryptorchidism in childhood. The results indicated that while all degrees of gonadal function occurred in these patients, the main adverse effect of cryptorchidism was on spermatogenesis. In some of the patients with oligospermia and normal Leydig cell function there was an isolated increase of basal serum FSH concentrations, suggesting a specific impairment of the testicular production of 'inhibin'. Gonadotrophin releasing hormone (LHRH) tests in these patients were compared to those in patients with normal basal gonadotrophins and to those with elevated basal LH and FSH concentrations. A selective exaggeration of the FSH response to exogenous LHRH in the group of patients with a monotropic elevation of FSH concentrations suggests that 'inhibin' modulates the secretion of FSH by an action on the pituitary rather than by modifying endogenous LHRH production by the hypothalamus.     

Seasonal changes in testicular structure and function and the effects of gonadotropins in the freshwater turtle,Chrysemys picta

Plasma testosterone was measured at stages during the reproductive cycle of control male turtles (Chrysemys picta) and following hypophysectomy and/or mammalian FSH or LH injection. Testosterone levels were highest in April and December when large Leydig cells were observed in the interstitium but the epithelium was inactive. During active spermatogenesis (July, October) plasma steroid levels were basal, and not significantly reduced by hypophysectomy. While LH injections had no effect, FSH was a potent stimulus to plasma testosterone in both intact and hypophysectomized turtles. Histologic observations during the testicular cycle and after hypophysectomy indicated that the tubular epithelium was dependent on endogenous pituitary hormone secretion but the interstitium did not atrophy during the experimental period. Injections of FSH in May increased testicular weight and caused disappearance of vacuoles and granules from apical portions of the Sertoli cell with a consequent reduction in cell height. Neither FSH nor LH had obvious effects on the morphology of the interstitium in control or hypophysectomized turtles either in July or November.     

5α-Reduced androgens and testicular function in the immature rat: Effects of 5α-androstan-1 7β-ol-3one (DHT) propionate and 5α-androstan-3α,17β-diol

Increasing doses of dihydrotestosterone propionate (DHTP) and 5α-androstan-3α,17β-diol (ADIOL) were given to 21-day-old rats for 10 days. Various parameters of reproductive function were assessed including testis weight, epididymal androgen binding protein (ABP) (Sertoli cell activity), plasma LH and FSH and the testicular levels of androstenedione (A), testosterone (T), dihydrotestosterone (DHT) and 5α-androstan-3α,17β-diol (ADIOL).In the control population, of the androgens measured, only the testicular concentration of DHT was highly correlated with epididymal ABP levels.After treatment with varying doses of DHTP, testis weight and epididymal ABP exhibited a biphasic response with maximum suppression occurring at the 100–250gmg/day dose level. Recovery of both of these parameters to control levels with 5,000–10,000 μg/day DHTP was associated with an increase in testicular DHT to normal or Supranormal levels. Plasma LH and FSH (pituitary function) and testicular A and T (Leydig cell function) were suppressed in a dose-dependent manner at doses including and higher than 50 μg DHTP/day. The testicular content of ADIOL was returned to control levels with 500 μg DHTP/day, when Sertoli cell function and spermatogenesis were still markedly suppressed. At DHTP doseshigher than 500 Jug/day, ADIOL was the predominant intratesticular androgen.Treatment with ADIOL also evoked a biphasic response from testis weight and epididymal ABP comparable to that observed with DHTP and testosterone propionate (TP) (Weddington et al., 1976). Doses from 20–500 μg/day resulted in a gradual, dose-dependent suppression of all the parameters studied. Administration of 1000 μg/day ADIOL returned the testicular ADIOL content to the control level. At the same dose, epididymal ABP, testis weight and the other intratesticular androgens were still maximally suppressed. Doses of 5000 and 10,000 μg/day ADIOL elevated the endogenous ADIOL in the testis to 4 and 25 times the normal level respectively. These higher doses also caused a dose-dependent increase in intratesticular DHT which was paralleled by an increase in epididymal ABP and testis weight. Even at the highest dose of ADIOL injected, DHT, epididymal ABP and testis weight did not completely return to normal levels.It is concluded that the previously observed stimulation of Sertoli cell function and spermatogenesis by androgens, in the rat, is mediated through DHT. Furthermore, the findings indicate that the apparent direct stimulation of Sertoli cell function by ADIOL is mediated through its conversion to DHT. The sensitivity of the testis to various androgens cannot be clearly interpreted on the basis of the administered doses, but only in relation to the levels of endogenous androgens in the testis achieved by the hormone treatment. In this regard, the study emphasizes the need for careful interpretation of data involving androgen treatment, especially ADIOL, and suggests that the relative potency of androgens in a bioassay system does not necessarily provide clear information about their relative potency at the target cell level.     

Increased serum inhibin B levels after varicocele treatment

OBJECTIVE: Inhibin B is secreted by Sertoli cells in response to FSH and is the major feedback regulator of FSH secretion in man. The serum inhibin B level has emerged as a good marker of spermatogenesis and Sertoli cell function. Varicocele has been associated with infertility and disturbed spermatogenesis. We have studied the effect of varicocele treatment on serum inhibin B levels, with the aim of investigating the effect on spermatogenesis and the involvement of the Sertoli cell in varicocele pathophysiology. DESIGN AND PATIENTS: In a pre-post test design, the effect of varicocele surgery on inhibin B levels was studied in 30 infertile men. MEASUREMENTS: Endocrinology (inhibin B, FSH, LH, SHBG and testosterone) and semen analysis (sperm concentration, motility and morphology). RESULTS: In men receiving varicocele treatment, a significant increase in serum inhibin B levels was observed from 133.9 +/- 13.4 pretreatment to 167.8 +/- 16.1 ng/l after treatment (mean +/- SEM, P < 0.0001). No significant changes were observed in serum levels of FSH, LH and testosterone. The serum SHBG level decreased from 32.9 +/- 3.5 to 28.6 +/- 3.4 nmol/l (mean +/- SEM, P = 0.04) and the free androgen index was significantly increased from 66 +/- 5.9 pretreatment to 85 +/- 6.8 after treatment (P = 0.02, mean +/- SEM). Semen analysis showed a significant improvement in sperm concentration, from 6.5 +/- 1.9 pretreatment to 19.3 +/- 4.9 x 106/ml after treatment (P = 0.003, mean +/- SEM), and in sperm motility from the baseline level of 17 +/- 3 to 32 +/- 4% after treatment (P = 0.001, mean +/- SEM). CONCLUSIONS: Varicocele treatment can increase serum inhibin B levels, indicating improvement of spermatogenesis and Sertoli cell function. This finding suggests that the pathophysiology of varicocele involves impairment of Sertoli cell function or a different distribution of germ cell stages.     

Hypothalamic-pituitary-gonadal function in men with cirrhosis of the liver.

Hypothalamic-pituitary-gonadal function was studied in 37 cirrhotic males, 25 of whom were alcoholic. Irrespective of aetiology, cirrhotic patients had significantly reduced free testosterone concentrations. Despite low free testosterone concentrations and reduced or absent spermatogenesis, basal levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) were normal in nearly all patients, suggesting impaired function of the hypothalamic-pituitary-gonadal axis. In 14 cirrhotic men, seven of whom had gynaecomastia, the ability of the pituitary to secrete LH and FSH in response to exogenous gonadotrophin releasing-hormone (LH/FSH-RH) was asssessed. A normal LH response to LH/FSH-RH was obtained in patients without gynaecomastia. An exaggerated LH response was found in four of seven with gynaecomastia, suggesting Leydig cell failure. The Leydig cell response to exogenous gonadotrophin in eight consecutive cirrhotic patients was probably abnormal but difficult to interpret as all but one were within conventionally accepted limits of normality. The patients without gynaecomastia gave a normal or minimally exaggerated FSH response to LH/FSH-RH. Six of seven with gynaecomastia gave a markedly exaggerated response suggesting failure of spermatogenesis, and all tested were either azoospermic of oligospermic. The single patient with a normal FSH response had a normal sperm count. The pituitary cells can therefore respond to LH/RSH-RH and the Leydig cells of the testes show some response to exogenous gonadotrophin. Similar abnormalities in hypothalamic-pituitary-gonadal function have recently been described in patients with normal liver function on chronic oestrogen therapy.     

Isolated follicle-stimulating hormone (FSH) deficiency in two infertile men without FSH β gene mutation: Case report and literature review

ObjectiveCongenital FSH deficiency is an exceptional cause of male infertility most often attributed to FSH β gene mutations. The few published cases report azoospermia, severe testicular hypotrophy and normal testosterone levels associated with normal virilization. We report the exploration of two young men aged 26 and 27 years with severe sperm abnormalities, moderate testicular hypotrophy and isolated FSH deficiency.MethodsSeveral FSH, LH, total testosterone and inhibin B assays and FSH β gene sequencing were performed.ResultsFSH was almost undetectable at baseline and poorly responsive to GnRH test, whereas LH was normal at baseline and increased after GnRH test. Testosterone levels were within the adult range, while inhibin B levels were upper-normal to high. No FSH β gene mutations were found. Exogenous FSH treatment was followed by spontaneous pregnancy in one case and required intra-cytoplasmic sperm injection (ICSI) in the other.ConclusionsThe paradoxical high levels of inhibin B reflect the presence of functional Sertoli cells and may explain the isolated FSH deficiency. An intra-gonadal factor stimulating inhibin B secretion is discussed.     

Serum inhibin levels in normal men and men with testicular disorders

Serum concentrations of inhibin, FSH and LH were measured in 39 normal men and 127 men with testicular disorders resulting in infertility. The infertile men were divided into groups on the basis of their mean sperm count, FSH levels and karyotype. The mean (+/- S.D) serum concentrations of inhibin in the normal men was 554 +/- 156 U/l and did not differ significantly from those groups with oligospermia, azoospermia or Klinefelter's syndrome. Combined analyses of all groups did not reveal any significant correlation between serum concentrations of inhibin and FSH or with any other parameter measured. Serum concentrations of FSH and LH were positively correlated, and Leydig cell dysfunction, as evidenced by increased serum LH levels, low testosterone levels or a declining testosterone/LH ratio were found with severe spermatogenic damage. The failure of serum concentrations of inhibin to correlate with those of FSH levels or the degree of testicular damage raise questions as to the clinical value of this parameter alone.     

Effects of an early postnatal treatment of hypogonadotropic hypogonadism with a continuous subcutaneous infusion of recombinant follicle-stimulating hormone and luteinizing hormone

BACKGROUND: The neonatal-midinfancy surge in pulsatile gonadotropin secretion is attributable to an increase in GnRH pulse amplitude and is associated with a rapid expansion of Leydig and Sertoli cell populations with concomitant surges in testosterone, inhibin, and anti-Mullerian hormone production as well as an increase in testicular volume. Boys with congenital hypogonadotropic hypogonadism (HH) do not activate these processes. A potential cause for azoospermia and infertility in adult life is deficient proliferation of immature Sertoli cells before and during puberty due to the absence of FSH. OBJECTIVE: The objective of the study was to investigate whether early postnatal continuous sc infusion of gonadotropins could mimic the physiological growth of testes and to evaluate responses of the Leydig and Sertoli cells to early gonadotropin replacement. DESIGN AND METHODS: Two neonates (P1 with hypotuitarism and P2 with HH) with micropenis and microorchidism were treated for 6 months with high doses of recombinant LH and FSH (a gift of Luveris and Gonal-F from Serono, Lyon, France) delivered sc with an insulin pump. RESULTS: Gonadotropin continuous sc infusion increased mean serum LH and FSH to normal or supranormal levels. Mean testosterone increased from undetectable levels to 7.6 and 5.2 nmol/liter, respectively, in P1 and P2. Inhibin B and anti-Müllerian hormone increased to normal levels. Mean testicular volume increased from 0.45 to 0.57 ml at birth to 2.10 ml at 7 months. Stretched penile length increased from 8 to 30 mm (P1) and 12 to 48 mm (P2). CONCLUSIONS: The present regimen induced physiological postnatal testes growth and high-normal activation of Leydig and Sertoli cells.     

Ageing, testicular tumours and the pituitary-testis axis in dogs

Dogs of different ages without testicular diseases were evaluated to study possible age-related changes in hormone concentrations in serum. Dogs with testicular tumours were also investigated to study the relation between tumour type and hormone concentrations; in this study, dogs with Sertoli cell tumours, Leydig cell tumours and seminomas were included. We measured testosterone, oestradiol, LH, FSH and inhibin-like immunoreactivity concentrations in peripheral venous and testicular venous blood of these animals. In normal dogs there appeared to be no age-related changes in the concentrations of the investigated hormones, except for a significant age-related decrease in oestradiol concentrations in testicular venous blood (P<0.02). Dogs with a Sertoli cell tumour had greater oestradiol concentrations and inhibin-like immunoreactivity in both peripheral and testicular venous blood than did dogs without a neoplasm (P<0. 05). Testosterone concentrations were reduced in dogs with Sertoli cell tumours, as were FSH and LH. Feminisation occurred in eight of 13 dogs with a Sertoli cell tumour and in two of 14 dogs with a Leydig cell tumour; it was accompanied by a significantly greater oestradiol concentration than in normal dogs and in dogs with Sertoli cell tumours without signs of feminisation. Dogs with a Leydig cell tumour had greater concentrations of oestradiol and inhibin-like immunoreactivity in both peripheral venous and testicular venous blood than did dogs without a neoplasm (P<0.05). The testosterone concentration in testicular venous blood of these dogs was lower than that in dogs with normal testes. The concentration of LH in peripheral venous blood was also reduced (P<0. 05). Hormone concentrations in dogs with a seminoma were not different from those in normal dogs. It was concluded that seminomas are not endocrinologically active. In contrast, both Sertoli cell tumours and Leydig cell tumours can cause increased oestrogen production leading to signs of feminisation. These tumours also have considerable amounts of inhibin-like immunoreactivity, but only in Sertoli cell tumours does this result in a reduction in FSH concentrations, suggesting that Sertoli cell tumours secrete dimeric inhibin, whereas Leydig cell tumours presumably produce loose alpha-subunits that cross-react in the inhibin assay but are not biologically active.     

Effect of cryptorchidism in the ram: changes in the concentrations of testosterone and estradiol and receptors for LH and FSH in the testis, and its histology

Cryptorchidism was induced in 5 pre-pubertal lambs and 7 adult rams, 5 months after surgery, testicular weight and membrane protein content were 4-fold lower than in the control. The total number of Leydig cells per testis was markedly decreased but their size was not changed. In contrast, the total number of Sertoli cells per testis was not affected but their nuclear size was smaller. Induced cryptorchidism had no effect on the length of seminiferous tubules; blood vessel volume was reduced; and the production of germ cells was completely disrupted. The number of LH receptors estimated per Leydig cell was not changed in pre-pubertal lambs but decreased 4-fold in adult rams. The number of FSH receptors calculated per Sertoli cell was reduced by 95% in both pre-pubertal and adult animals. No effect on the binding affinities of LH (Ka = 1 X 10(10) M-1) and FSH (Ka = 4.5 X 10(9) M-1) to their testicular receptors was observed. Although testicular concentrations of testosterone and estradiol-17 beta were increased, the total content of testosterone within the testis was increased only in pre-pubertal lambs. The estimated ratio of testosterone per Leydig cell was higher in cryptorchid animals than in controls, suggesting that, despite their reduction in number and the decrease of LH receptors, the Leydig cells of cryptorchid rams have an enhanced steroidogenic capacity. This study also confirms the important dysfunction of the Sertoli cells in cryptorchid rams.     

Elevated steroidogenesis,defective reproductive organs,and infertility in transgenic male mice overexpressing human chorionic gonadotropin

We previously developed a transgenic (TG) mouse model that overexpresses the human chorionic gonadotropin (hCG) beta-subunit under the universal human ubiquitin C promoter, displaying in males a modest 3-fold increase in circulating levels of LH/hCG bioactivity. The males were fertile and presented with a mild reproductive phenotype. To achieve higher levels of hCG, a double TG model was generated by cross-breeding the hCG beta-expressing mice with another TG line harboring a ubiquitin C/common alpha-subunit fusion gene. The double-TG mice expressed excessive levels of dimeric hCG, with 2000-fold elevated circulating LH/hCG bioactivity. These male mice were infertile, primarily due to inability to copulate, and they showed enhanced testicular androgen production despite clear down-regulation of LH/hCG receptors. Their intratesticular inhibin B was unaltered, but serum FSH was markedly reduced. Apparently the chronic hCG hyperstimulation led to focal Leydig cell proliferation/hypertrophy at 6 months of age, but failed to promote testicular tumors. Even though full spermatogenesis occurred in most of the seminiferous tubules, progressive tubule degeneration was apparent as the males grew older. The prostate and seminal vesicles were enlarged by distension of glandular lumina. Functional urethral obstruction was indicated by distension and sperm accumulation in distal vas deferens as well as by dilated urinary bladder and enlarged kidneys. The abnormal function of accessory sex glands and/or lower urinary tract as a consequence of the disturbed sex hormone balance or direct action of hCG may be the main cause of infertility in this model. The present study provides in vivo evidence that exposure of male mice to chronically elevated levels of hCG severely affects their urogenital tract function at multiple sites and causes infertility, but, unlike in LH/hCG overexpressing female mice, it is not tumorigenic.     

Do testicular opiates regulate Leydig cell function?

beta-Endorphin is believed to be synthesized in testicular Leydig cells. To gain more information about the role of this and other endogenous opioid peptides in the testis, opiate antagonists (naloxone and nalmefene, 100 micrograms/testis) were administered intratesticularly to hemicastrated adult rats. Leydig cell function was evaluated by measurement of serum testosterone and testosterone production in vitro. Estimation of androgen binding protein (rABP) was used as an index of Sertoli cell function. Serum testosterone was reduced significantly by intratesticular administration of naloxone and nalmefene in treated animals. Systemic administration of these antagonists had no effect at the doses used. Testes from treated animals incubated in vitro with or without hCG produced significantly less testosterone than vehicle-treated control testes. Hemicastration reduced rABP synthesis and secretion; however, treatment with opiate antagonists did not alter the amount of this protein in the serum or epididymides of these rats. These observations suggest that endogenous testicular opiates modulate testosterone secretion by Leydig cells.     

Studies of the human testis. XVII. Gonadotropin regulation of intratesticular testosterone and estradiol in infertile men

Serum levels of LH and FSH and the intratesticular concentrations of testosterone (T) and estradiol (E) were measured in biopsy tissue from 40 infertile men, aged 21-36 yr, of whom 21 were oligospermic men with varicocele and 19 were men with idiopathic oligospermia. Intratesticular T and E concentrations were negatively correlated (P less than 0.001) with testicular volumes, as measured with a calibrated orchidometer, suggesting that differences in measured intratesticular steroid levels in part reflect altered relative Leydig cell density as seminiferous tubular volume changes. To gather information about the regulation of intratesticular T and E by gonadotropins, we calculated an index of intratesticular steroid content by multiplying steroid concentration by testicular volume and compared these values with circulating LH and FSH levels. Highly significant positive correlations were found between both serum LH and FSH and intratesticular E content and between LH and FSH and intratesticular T content. Multivariant stepwise regression analysis revealed that while serum FSH is a strong predictor of intratesticular E (r = 0.72; P less than 0.001), serum LH is not (partial r = 0.00 when controlling for the influence of FSH). Instead, the apparent relationship between Serum LH and intratesticular E results from the highly positive correlation between serum LH and FSH in the patients studied (r = 0.71; P less than 0.001). Similarly, circulating LH levels are independently related to intratesticular T content (r = 0.67; P less than 0.001), whereas the relationship between FSH and T is indirect (partial r = 0.06 when controlling for the influence of LH). We believe that these associations suggest that the major regulator of intratesticular T content is LH and that FSH may be the important gonadotropin regulating intratesticular E.     

The detrimental effects of spinal cord injury on spermatogenesis in the rat is partially reversed by testosterone, but enhanced by follicle-stimulating hormone

Our previous studies have demonstrated that impaired spermatogenesis during the acute phase of spinal cord injury (SCI) is preceded by a transient (but significant) suppression of serum FSH, LH, and testosterone (T) concentrations. It is hypothesized that hormonal deprivation may impair Sertoli cell function, leading to the loss of spermatogonia, degeneration of spermatogenic cells, and eventual regression of the seminiferous epithelium. The current study examined the efficacy of exogenous T and FSH in the maintenance of spermatogenesis and Sertoli cell functions in SCI rats. Implantation of T capsules (TC, 2 x 5 cm) attenuated some of the spermatogenic lesions and maintained qualitatively complete spermatogenesis in all SCI rats 4 weeks after the surgery. In contrast, daily injections of 0.1 U of FSH alone, or in combination with TC implants, paradoxically enhanced the regression of spermatogenesis in SCI rats. At this time, the numbers of Aal, A1, and B spermatogonia and preleptotene spermatocytes in SCI rats have decreased by 25-30%. Though not prevented by TC implants, the decrease in Aal and A1 spermatogonia was attenuated by FSH alone but was further enhanced when FSH-treated rats also received TC implants. The intratesticular T concentration in untreated and FSH-treated SCI rats was not different from that of sham control rats, but it decreased by more than 95% in those SCI rats given TC implants alone. These results demonstrate that impairment of spermatogenesis during the acute phase of SCI is not related to the availability of FSH and/or T. Northern blot analysis revealed an increase in androgen receptor messenger RNA (mRNA) in the testis of SCI rats; this increase was prevented by TC implants but persisted when FSH was also given. In contrast, the levels of FSH-receptor, androgen binding protein, and transferrin mRNA were not affected by SCI but were significantly higher in those SCI rats given FSH alone or in combination with TC. TC implants alone suppressed mRNA levels of transferrin in testes of SCI rats, without concomitant change in those for FSH-receptor and ABP. The changes in Sertoli cell responses to FSH and T, and perhaps other hormones, may alter signal events elicited by these hormones, thus contributing to abnormal epithelial environments and regression of spermatogenesis. Maintenance of spermatogenesis in SCI rats by exogenous T suggests the feasibility of using exogenous hormones to impede the detrimental effects of SCI on spermatogenesis. This approach may have clinical applicability for the preservation of spermatogenic functions in SCI men.     

Plasma 5 alpha-dihydrotestosterone and testosterone in the bullfrog, Rana catesbeiana: stimulation by bullfrog LH.

Effects of purified bullfrog (Rana catesbeiana) LH and FSH on plasma levels of the androgens, testosterone (T), and 5α-dihydrotestosterone (DHT), were studied using adult male bullfrogs. Rana LH was considerably more potent than Rana FSH in stimulating increased plasma androgen levels in hypophysectomized and intact animals. Simultaneous injection of Rana FSH or ovine PRL with Rana LH, over a 10-day period, did not alter the LH-induced increase in plasma androgens. More DHT than T was present in plasma after LH injection. Castration abolished plasma DHT and greatly reduced plasma T. Results indicate that DHT is a major testicular steroid, and that testicular androgen secretion is stimulated primarily by LH in the bullfrog.     

Klinefelter syndrome

Klinefelter syndrome (KS) is the most common genetic form of male hypogonadism, but overt phenotype becomes evident only after puberty. During childhood, and even during early puberty, pituitary-gonadal function in 47,XXY subjects is relatively normal, but from midpuberty onwards, FSH and LH levels increase to hypergonadotropic levels, inhibin B decreases to undetectable levels, and testosterone levels after some increase plateau at low-normal levels for healthy adult men. Hence, most adult KS males display a clear hypergonadotropism with a varying degree of androgen deficiency; subsequently testosterone substitution therapy is widely used to prevent symptoms and sequels of androgen deficiency. Testicular biopsies of prepubertal KS boys have shown preservation of seminiferous tubules with reduced numbers of germ cells, but Sertoli and Leydig cells have appeared normal. The testes in the adult KS male are characterized by extensive fibrosis and hyalinization of the seminiferous tubules, and hyperplasia of the interstitium. However, the tubules may show residual foci of spermatogenesis. Introduction of testicular sperm extraction (TESE) in combination with intracytoplasmic sperm injection (ICSI) techniques has allowed non-mosaic KS males to father children.