Testicular Hormone Secretion Research Articles

Perspectives in Pediatric Pathology, Chapter 6. Male Undermasculinization.

Normal male development requires three conditions: (1) adequate differentiation of the fetal testis; (2) synthesis and secretion of testicular hormones; and (3) effective action of these hormones on target organs. This requires the combined action of the inhibitory anti-müllerian hormone (AMH, secreted by Sertoli cells) to block the development of the uterus and fallopian tubes from the müllerian duct, together with the trophic stimulus of testosterone (a Leydig cell product), which leads to virilization of the wolffian ducts. Additionally, the development of external genitalia depends on the conversion of testosterone to dihydrotestosterone by the enzyme 5-α-reductase. Failure of any of these mechanisms leads to deficient virilization or the so-called "male pseudohermaphroditism" syndromes.

Effects of Crude Extract of Dry Fruits of Piper guineense on Male Fertility Parameters of Adult Sprague Dawley Rats

Objective: To study the effect of aqueous extract of dry fruits of Piper guineense on male fertility parameters of adult male Sprague Dawley rats. Materials and Methods: 30 adult male Sprague Dawley rats weighing between 120g -150g were used. They were divided into three (3) groups. The control (group A), Short term treatment Group A (Group B) received 200 mg/kg of extract for 4 weeks (28 days) and long term treatment (Group C) received 200 mg/kg of extracts for 8 weeks (56 days). Extract was given via gastric intubation. The controls as well as treated animals were allowed free access to pelleted feed and water ad libitum. Original Research Article Memudu et al.; EJMP, 5(3): 297-303, 2015; Article no.EJMP.2015.029 298 The animals were sacrificed and blood taken for serum biochemical analysis. Testicular weight was taken and recorded. Caudal epididymis excised for semen analysis. Results: There was an increase in animal body weight gained throughout the duration of the experiment as compared with the control. There was also a significance increase in testicular weight. Serum testosterone level increased in treated groups. Semen analysis reveals normal parameters no oligospermic or azoospermic condition was detected. Sperm morphology was normal and no teratozoospermic sperm found. Conclusion: The aqueous extract of Piper guineense at dose of 200mg/kg for 4 weeks and 8 weeks respectively had a positive impact on male fertility parameters. From results obtained, Piper guineese enhances testicular hormone secretion. This study revealed no deleterious effects of aqueous extraction of dry fruits of Piper guineense on male fertility.

Spreading the clinical window for diagnosing fetal-onset hypogonadism in boys.

In early fetal development, the testis secretes – independent of pituitary gonadotropins – androgens and anti-Müllerian hormone (AMH) that are essential for male sex differentiation. In the second half of fetal life, the hypothalamic–pituitary axis gains control of testicular hormone secretion. Follicle-stimulating hormone (FSH) controls Sertoli cell proliferation, responsible for testis volume increase and AMH and inhibin B secretion, whereas luteinizing hormone (LH) regulates Leydig cell androgen and INSL3 secretion, involved in the growth and trophism of male external genitalia and in testis descent. This differential regulation of testicular function between early and late fetal periods underlies the distinct clinical presentations of fetal-onset hypogonadism in the newborn male: primary hypogonadism results in ambiguous or female genitalia when early fetal-onset, whereas it becomes clinically undistinguishable from central hypogonadism when established later in fetal life. The assessment of the hypothalamic–pituitary–gonadal axis in male has classically relied on the measurement of gonadotropin and testosterone levels in serum. These hormone levels normally decline 3–6 months after birth, thus constraining the clinical evaluation window for diagnosing male hypogonadism. The advent of new markers of gonadal function has spread this clinical window beyond the first 6 months of life. In this review, we discuss the advantages and limitations of old and new markers used for the functional assessment of the hypothalamic–pituitary–testicular axis in boys suspected of fetal-onset hypogonadism.

Two Families with Normosmic Congenital Hypogonadotropic Hypogonadism and Biallelic Mutations in KISS1R (KISS1 Receptor): Clinical Evaluation and Molecular Characterization of a Novel Mutation

Context KISS1R mutations have been reported in few patients with normosmic congenital hypogonadotropic hypogonadism (nCHH) (OMIM #146110).ObjectiveTo describe in detail nCHH patients with biallelic KISS1R mutations belonging to 2 unrelated families, and to functionally characterize a novel KISS1R mutation.ResultsAn original mutant, p.Tyr313His, was found in the homozygous state in 3 affected kindred (2 females and 1 male) from a consanguineous Portuguese family. This mutation, located in the seventh transmembrane domain, affects a highly conserved amino acid, perturbs the conformation of the transmembrane segment, and impairs MAP kinase signaling and intracellular calcium release. In the second family, a French Caucasian male patient with nCHH was found to carry two recurrent mutations in the compound heterozygous state (p.Leu102Pro/Stop399Arg). In this man, pulsatile GnRH (Gonadotropin Releasing Hormone) administration restored pulsatile LH (Luteinizing Hormone) secretion and testicular hormone secretion. Later, long-term combined gonadotropin therapy induced spermatogenesis, enabling 3 successive pregnancies that resulted in 2 miscarriages and the birth of a healthy boy.ConclusionWe show that a novel loss-of-function mutation (p.Tyr313His) in the KISS1R gene can cause familial nCHH, revealing the crucial role of this amino acid in KISS1R function. The observed restoration of gonadotropin secretion by exogenous GnRH administration further supports, in humans, the hypothalamic origin of the gonadotropin deficiency in this genetic form of nCHH.

Pineal and gonadal influences on ultradian locomotor rhythms of male Siberian hamsters

The extent to which changes in ultradian and circadian rhythms (URs and CRs) reflect seasonal variations in pineal melatonin secretion was assessed in male Siberian hamsters transferred from long to short day lengths. The period of the locomotor activity UR increased from 2.5h in long days to 4.5h in short day lengths, but this and most other features of the short-day ultradian phenotype were unaffected by pinealectomy; only the short-day increase in UR amplitude was counteracted by pineal extirpation. Virtually all UR components were unaffected by gonadectomy or replacement testosterone or estradiol treatment; changes in testicular hormone secretion appear insufficient to account for seasonal fluctuation in URs. Pinealectomy did not affect activity onsets and offsets or phase angles of CR entrainment in short and long day lengths; the duration of nocturnal activity was equivalently longer in short than long days in both pinealectomized and pineal-intact hamsters. CR robustness of pinealectomized hamsters in short days was intermediate between values of long-day and short-day sham-pinealectomized males. Hourly nocturnal locomotor activity was markedly reduced in SD, and this effect was completely reversed by PINx. We conclude that seasonal transitions in UR and CR waveforms controlled by day length are mediated primarily by melatonin-independent mechanisms, with lesser contributions from melatonin-dependent processes. Most seasonal changes in ultradian and circadian rhythms in males of this species are not influenced by gonadal hormones. URs may allow animals to respond appropriately to changing environmental contingencies. In winter reduced activity combined with temporal restructuring of activity to include longer intervals of rest may be adaptive in maintaining body temperature at lower values and down-regulating energy expenditure when above ground temperatures are extremely low.

Testicular Anti-Müllerian Hormone: Clinical Applications in DSD

Male fetal sexual differentiation of the genitalia is driven by Leydig cell-secreted androgens and Sertoli cell-secreted anti-Müllerian hormone (AMH). Disorders of sex development (DSD) may be due to abnormal morphogenesis of genital primordia or to defective testicular hormone secretion or action. In dysgenetic DSD, due to an early fetal-onset primary hypogonadism affecting Leydig and Sertoli cells, the fetal gonads are incapable of producing normal levels of androgens and AMH. In non-dysgenetic DSD, either Leydig cells or Sertoli cells are affected but not both. Persistent Müllerian duct syndrome (PMDS) may result from Sertoli cell-specific dysfunction due to mutations in the AMH gene; these patients have Fallopian tubes and uterus, but male external genitalia. In DSD due to insensitivity to testicular hormones, fetal Leydig and Sertoli cell function is normal. Defective androgen action is associated with female or ambiguous genitalia whereas insensitivity to AMH results in PMDS with normal serum AMH. Clinical and biological features of PMDS due to mutations in the genes coding for AMH or the AMH receptor, as well as genetic aspects and clinical management are discussed.

Vasoconstriction of Testicular Arterioles is Decreased with Advancing Age but Minimally Affected by Endurance Training

Testosterone declines at a predictable rate in men after the 4th decade of life. This decline is associated with decreased parameters of fertility and many deleterious symptoms of aging. Both testicular hormone secretion and spermatogenesis are extremely sensitive to changes in blood flow. PURPOSE: To determine whether 1) there are age-associated vasomotor perturbations of the testicular resistance vasculature, and 2) chronic endurance exercise influences vasomotor characteristics of the testicular resistance vasculature. METHODS: Young (Y; 5-6mo) and old (O; 22-24mo) male Fischer-344 rats were divided into sedentary (YSed, n=20; OSed, n=20) and exercise-trained (YET, n=11; OET, n=12) groups. ET rats completed 10wk of treadmill running while Sed rats remained sedentary for 10wk. Testicular arterioles (max diameter ∼150μm) were then isolated, cannulated, warmed (34°C) and pressurized (70cm H20) for in-vitro study of various vasoconstrictor (VC) stimuli. RESULTS: VC to norepinephrine (NE) was decreased in OSed (47.6 ± 2.4%) compared to YSed (58.1 ± 2.1%). Beta adrenergic receptor blockade reduced VC to NE in OSed (38.4 ± 3.2%). With the addition of nitric oxide synthase (NOS) inhibition to beta blockade, VC to NE was increased in YSed (69.3 ± 2.7%) but not OSed. VC to the alpha-1 adrenergic agonist phenylephrine was higher in YSed (51.1 ± 3.3%) than OSed (36.3 ± 4.4%). There were no age-associated differences in myogenic autoregulation or passive distension to increasing transmural pressure. The only significant effect of exercise training was increased VC to NE in the presence of beta blockade plus NOS inhibition in OET (57.9 ± 5.6%) vs OSed (44.1 ± 2.4%). CONCLUSIONS: Sedentary aging was associated with decreased VC to NE, due, in part, to reduced alpha-1 adrenergic VC which was not restored with ET. Failure to maintain the normally high testicular precapillary vascular resistance with advancing age may contribute to reduced fertility parameters and hormone production by elevated capillary filtration and subsequent washout of the hormone-rich milieu which is essential to normal Leydig and Sertoli cell function.

Effect of a Single Injection of Human Chorionic Gonadotropin (hCG) on Testicular Hormones and Gonadotropins in the Thoroughbred Stallion

The changes in testicular and pituitary functions in response to human chorionic gonadotropin (hCG) in the breeding and non-breeding season were investigated and compared in the Thoroughbred stallion. Five mature Thoroughbred stallions ranging in ages from 7 to 21 years were injected in May (breeding season) and October (non-breeding season). All animals received an intramuscular injection of 5,000 IU hCG in the experiments. Peripheral blood samples were collected in heparinized tubes from the jugular vein for hormonal assays just before the injection (Day 0) and at a daily interval for five days following the injections (Days 1, 2, 3, 4 and 5). Basal levels of immunoreactive (ir) inhibin, testosterone, estradiol-17β, FSH and LH were higher in the breeding season than in the non-breeding season. There were significant differences in estradiol-17β, FSH and LH between the two seasons. Ir-inhibin exhibited significant increases on Day 2 after the hCG treatment in the non-breeding season, though there was no change in the breeding season. Plasma levels of testosterone showed remarkable increases after the hCG injection in both seasons. The peak levels of plasma testosterone were observed on Days 2 and 3 in the breeding and non-breeding seasons. Plasma estradiol-17β was significantly higher than the basal level on Day 3 in the non-breeding season, whereas there was no change in the breeding season. Plasma levels of FSH declined from Day 1 to Day 3, then recovered to the basal level (Day 0) on Day 4 after hCG treatment in the breeding season, whereas there was no change in the non-breeding season. Circulating LH showed a significant decrease on Day 3 compared to the based level in the breeding season, but no significant change in the non-breeding season after a treatment of hCG. A significant negative correlation was observed between testosterone and FSH in the breeding season. In conclusion, hCG treatment stimulates secretion of testicular hormones and these testicular hormones temporarily suppress secretion of gonadotropins from the pituitary gland. These results also suggested that Leydig cells of thoroughbred stallion testes have LH receptors in the non-breeding season, the same as in the breeding season.

Expression and Localization of Growth Factors and their Receptors in the Mammalian Testis. Part I: Fibroblast Growth Factors and Insulin‐Like Growth Factors

It is now well established that normal development and function of testis are mediated by endocrine and paracrine pathways including hormones, growth factors and cytokines as well as by direct cell-to-cell contacts depending on tight, adhering and gap junctions. In the last two decades, several growth factors were identified in the testis of various mammalian species. Growth factors are shown to promote cell proliferation, regulate tissue differentiation, and modulate organogenesis. Interestingly, most of these peptides are expressed not only in the adult mammalian testis during spermatogenesis but also during testicular morphogenesis in prenatal and postnatal life. Our study was launched to provide an overview of the expression, localization, and putative physiological roles of growth factors and their receptors in the mammalian testis. The growth factors considered in this part of our review are fibroblast growth factors and insulin-like growth factors. These factors are found in testicular cells in prenatal, postnatal, and adult animals and are implicated in the regulation of important testicular activities including testicular cord morphogenesis, modulation of testicular hormone secretion and control of spermatogenesis.

Photoperiodic regulation of circulating leukocytes in juvenile Siberian hamsters: mediation by melatonin and testosterone.

The reproductive system of Siberian hamsters (Phodopus sungorus) undergoes rapid phenotypic responses to changes in day length that occur around the time of weaning. The present experiments tested whether the immune system of Siberian hamsters is similarly photoperiodic early in life and whether photoperiodic changes in melatonin or gonadal hormone secretions mediate any such responses to day length. Circulating blood leukocyte concentrations (WBC) were measured in juvenile male Siberian hamsters that were gestated in long-days (LD), transferred to short-days (SD) on the day of birth, and subsequently either remained in SD or were transferred from SD to LD at 18 days of age (day 18). WBC values were comparable between LD and SD hamsters on day 18. Between day 18 and day 32, SD hamsters exhibited a 3-fold increase in WBC, whereas LD hamsters failed to undergo a significant increase in WBC during this interval. WBC of LD hamsters was significantly lower than that of SD hamsters on day 25 and on day 32. In LD housed males, peripheral injections of melatonin delivered so as to extend the nocturnal duration of elevated endogenous melatonin secretion (i.e., provided in late afternoon) on days 18-31 increased WBC as measured on day 32. Peripubertal (day 17) gonadectomy abolished the immunosuppressive effect of LD exposure on WBC, and treatment with silastic implants containing testosterone suppressed WBC independent of photoperiod treatment. These data indicate that juvenile Siberian hamsters are immunologically responsive to photoperiod and that the leukocyte responses to day length are the result of melatonin-mediated effects of photoperiod on testicular hormone secretion.

Effects of anabolic steroid (19-nortestosterone) on the secretion of testicular hormones in the stallion.

The aim of this study was to clarify the effect of anabolic steroids on the testicular endocrine function of mature stallions. Mature thoroughbred stallions were treated with 800 mg nandrolone decanoate every 3 weeks for 3 months. After the first treatment, plasma concentrations of LH, immunoreactive inhibin and testosterone decreased rapidly to the nadir. These hormones were maintained at significantly lower concentrations compared with concentrations in intact stallions. Histology of the testicular tissue indicated the arrest of advanced spermatogenesis in the seminiferous tubules and a severe depletion of the number of Leydig cells in the interstitial compartment as a result of treatment. Most of the immunopositive cells for the inhibin alpha-subunit and steroidogenesis enzymes in the interstitial compartment decreased below detectable amounts, whereas immunopositive reactions of inhibin alpha-subunit in the seminiferous tubules were clearly observed. In conclusion, the treatment of mature stallions with nandrolone decanoate caused a decrease in the secretion of ir-inhibin and testosterone from the testis, the depletion of the number of Leydig cells and a decrease below detectable amounts of inhibin alpha-subunit and steroidogenesis enzymes. The concentration of ir-inhibin in the peripheral blood may be a useful marker for the examination of testicular activity in stallions being treated with anabolic steroids.

Does Testosterone Diffuse Down the Wolffian Duct During Sexual Differentiation?

Purpose Sexual differentiation in gonadal dysgenesis is commonly asymmetrical. In patients with true hermaphroditism there may be an ovary and mullerian duct on 1 side, and a testis and wolffian duct on the other side. Such asymmetry suggests that testicular hormones only act locally at this early stage of sexual differentiation. We tested the hypothesis that testosterone reaches the wolffian duct by transport down the duct rather than by simple diffusion. Materials and Methods Mouse 14-day urogenital ridges were placed in organ culture and microinjected with testosterone-albumin-fluorescein isothiocyanate. Results At 17 hours fluorescence was found throughout the wolffian duct and by 48 hours it was maximal in the dilated caudal end. Conclusions Our results support the hypothesis that androgens may be transported along the wolffian duct. Secretion of testicular hormones into the wolffian duct may maintain hormone levels in the biologically active range.

Sexual and aggressive behaviour of adult male marmosets ( Callithrix jacchus) castrated neonatally, prepubertally, or in adulthood

During early postnatal development, males of some primate species exhibit higher levels of plasma testosterone than females. The possible significance of this for behavioural development was examined in male marmosets castrated neonatally (NC), prepubertally (PC), or in adulthood (AC) and reared in their natal groups. Age-matched intact (AI) adult males served as controls. All males were removed from their natal groups as adults for pair testing with unfamiliar conspecific males and females. NC males did not mount, but were frequently aggressive during tests with females. NC males also elicited aggression from females but rarely from intact males. PC and AC males attempted copulation during the majority of tests with females; less aggression occurred but more so in tests with PC males than between females and AC males. Aggression between PC or AC males and intact males was much more frequent than when NC males met intacts in paired encounters. Results show that secretion of testicular hormones during infancy in male marmosets has important effects upon the development of sexual and aggressive behaviour. Castration in infancy has measurably different effects upon behavioural development than castration performed later in life (prepubertally or in adulthood).

Physiopathologic aspects of Leydig cell function in varicocele patients.

Leydig cell function was studied in 108 varicocele (V) patients with a mean age of 30.9 years, and a control group (C) of 46 men with a mean age of 30 years. Plasma gonadotropin levels were determined before and after GNRH stimulation. Testosterone (T), 17-OH-progesterone (17-OH-P), dihydrotestosterone (DHT) and estradiol (E2) were also assayed. Mean plasma T levels were significantly decreased in varicocele patients (V = 416 +/- 12.9, n = 106; C = 487 +/- 19.9, n = 40; P less than 0.01), while the basal 17-OH-P/T ratio was significantly increased (V = 0.38 +/- 0.02, n = 56; C = 0.28 +/- 0.02, n = 40; 0.02 greater than P greater than 0.01) and remained higher after hCG stimulation (P less than 0.01). No significant differences in mean sex steroid levels were observed when comparing varicocele patients with normal sperm counts (VN) and those who had oligozoospermia (VO). There was a significant negative linear correlation between age and 17-OH-P (n = 56; r = -0.47; P less than 0.01) and T values (n = 106; r = 0.27; P less than 0.01) in varicocele patients, which contrasted with the absence of any significant correlation with age in the controls. These data suggest that the duration of idiopathic varicocele influences testicular hormone secretion.

Effects of cimetidine on pituitary function: Alterations in hormone secretion profiles.

Cimetidine, an H2 receptor antagonist, was given for 6 weeks to six normal male volunteers to study the effects on pituitary, adrenal, thyroid, and testicular hormone secretion. Patients were studied before (day 1) and after (day 42) cimetidine (300 mg four times daily) therapy, and four of the six were restudied after discontinuing cimetidine for 1 month (day 72). Basal TSH concentrations and responses to TRH administration as well as T3 RIA and T4 resin uptakes did not change during or after cimetidine therapy. The diurnal rhythm of plasma cortisol and maximum cortisol response to insulin (0.15 u/kg) were similar on days 1 and 42, but urinary free cortisol excretion fell 31% (Pless than 0.01). Response of GH to exercise, 100 g carbohydrate ingestion and insulin were unchanged, but mean nocturnal GH secretion decreased 33% (P less than 0.025) on cimetidine, and returned to baseline on day 72. The 24-h plasma prolactin profile was unchanged as was the prolactin response to insulin and TRH stimulation. Plasma FSH was not altered, but mean LH concentrations decreased 20% on cimetidine and continued to decline (45% of day 1 levels) after discontinuation of cimetidine (P less than 0.01). Spontaneous LH pulse amplitude declined slightly on day 42, but became significantly lower on day 72 (P less than 0.05). Peak LH responses t gonadotropin-releasing hormone were also reduced on cimetidine therapy (P less than 0.02). Plasma testosterone concentrations did not change but plasma oestradiol concentrations were 38% lower (P less than 0.025) after cimetidine was discontinued. H2 histamine receptors are involved in the control of multiple hormone secretory patterns and blockade of these receptors by cimetidine alters hormone profiles. These changed patterns have to be considered in the interpretation of hormone measurements in patients receiving cimetidine therapy.

REGULATION OF PLASMA OESTROGENS IN NORMAL ADULT MALES

ABSTRACT The response of plasma oestradiol (Oe2), oestrone (Oe1), testosterone (T) and cortisol to dexamethasone and ACTH administration in normal adult males was ascertained. After an oral dose of 1.5 mg dexamethasone Oe1 decreased from 2.51 to 1.85 ng/100 ml (74 % of the control level, mean of 15 subjects) over night and after continuing the dexamethasone administration for two more days (twice daily 1.5 mg) Oe1 decreased to 1.30 ng/100 ml (52 %). Oe2 (control level 1.71 ng/100 ml) and T (678 ng/100 ml) did not change over night, but at the end of the test Oe2 decreased to 84 % and T to 91 % of the control level. After a single im injection of 2 mg β 1–24 cortrophin Oe1 increased 1.9 times (mean of 13 subjects) without further increase during two more days of treatment (twice daily 1 mg), while Oe2 did not change over night and decreased to 75 % of the control level at the end of the test. Under ACTH T decreased to 66% of the control level over night and to 50% at the end of the test indicating a suppression of the testicular hormone secretion. From these results and those reported previously it was concluded that the testicular hormone secretion influences mainly Oe2 in peripheral plasma, while Oe1 depends mainly on the adrenal hormone secretion.