Regulation Of Male Reproductive Function Research Articles

Asprosin regulates male reproduction in teleosts: an in vitro study in Channa punctata.

The novel adipokine asprosin, produced by the furin enzymatic cleavage of profibrillin 1 protein (encoded by the Fbn1 gene), is implicated in regulating many physiological functions, including reproduction in mammals. In males, asprosin is reported to increase sperm density, sperm motility, and steroid production by interacting with Olfr734, which belongs to the G-protein-coupled receptor family (GPCR). In 2023, our group predicted and characterized asprosin in silico for the first time and demonstrated the robust expression of fbn1, and furin in the gonads of teleost spotted snakehead (ss) Channa punctata. Taking it forward, in the current study, we have investigated the effect of asprosin on the testicular functions of the spotted snakehead. As C. punctata is a seasonal breeder, the reproductive-phase-dependent expression of fbn1 in the testis was analyzed, showing significant upregulation during the preparatory and post-spawning phases. Additionally, bacterially overexpressed recombinant asprosin of C. punctata was purified to study the effect of ss asprosin on gametogenesis and steroidogenesis. Ex vivo treatment with recombinant asprosin resulted in significant upregulation of spermatogenic marker genes pcna, aldh1a2, cyp26a1, and sycp3. Asprosin also enhanced the gene expression of gonadotropin receptors, as well as sex steroid receptors, in addition to steroidogenic genes star and cyp17a1. Further exploring the downstream signaling cascade, the second messenger of GPCRs, cAMP levels following asprosin treatment were analyzed. Asprosin treatment prominently enhanced cAMP levels, thereby indicating the involvement of GPCR in the transduction of asprosin action. Hence, the study elucidates the regulation of male reproductive function by asprosin in spotted snakeheads.

Effect of Humanin and MOTS-c on ameliorating reproductive damage induced by prepubertal cyclophosphamide chemotherapy in male mice

Male patients who undergo prepubertal chemotherapy face the dual problems of fertility preservation in adulthood, including low testosterone, hypersexual function, and infertility. Humanin, as a small polypeptide coded within the mitochondrial DNA, with the mitochondrial short open reading frame named MOTS-c, both was believed to regulate mitochondrial homeostasis, be anti-inflammatory, improve metabolism, anti-apoptosis, and multiple pharmacological effects. However, there exists little evidence that reported Humanin and MOTS-c 's effects on moderating male spermatogenic function of patients after prepubertal chemotherapy. Here, we found that in vivo, mitochondrial polypeptides Humanin analog (HNG) and MOTS-c efficaciously protected the testicular spermatogenic function from reproductive injury. Moreover, transcriptomic sequencing analysis was performed to verify the differentially expressed genes such as Piwil2, AGT (angiotensinogen), and PTGDS (glycoprotein prostaglandin D2 synthase), which are related to the regulation of male reproductive function of male mice induced by prepubertal chemotherapy. Collectively, our data revealed that both Humanin analogs HNG and MOTS-c are the feasible approaches attached to the protective effect on the male reproductive function damaged by prepubertal chemotherapy.

Review of the Role of Ferroptosis in Testicular Function.

Iron is an important metal element involved in the regulation of male reproductive functions and has dual effects on testicular tissue. A moderate iron content is necessary to maintain testosterone synthesis and spermatogenesis. Iron overload can lead to male reproductive dysfunction by triggering testicular oxidative stress, lipid peroxidation, and even testicular ferroptosis. Ferroptosis is an iron-dependent form of cell death that is characterized by iron overload, lipid peroxidation, mitochondrial damage, and glutathione peroxidase depletion. This review summarizes the regulatory mechanism of ferroptosis and the research progress on testicular ferroptosis caused by endogenous and exogenous toxicants. The purpose of the present review is to provide a theoretical basis for the relationship between ferroptosis and male reproductive function. Some toxic substances or danger signals can cause male reproductive dysfunction by inducing testicular ferroptosis. It is crucial to deeply explore the testicular ferroptosis mechanism, which will help further elucidate the molecular mechanism of male reproductive dysfunction. It is worth noting that ferroptosis does not exist alone but rather coexists with other forms of cell death (such as apoptosis, necrosis, and autophagic death). Alleviating ferroptosis alone may not completely reverse male reproductive dysfunction caused by various risk factors.

Selective Depletion of Adult GFAP-Expressing Tanycytes Leads to Hypogonadotropic Hypogonadism in Males.

In adult mammals, neural stem cells are localized in three neurogenic regions, the subventricular zone of the lateral ventricle (SVZ), the subgranular zone of the dentate gyrus of the hippocampus (SGZ) and the hypothalamus. In the SVZ and the SGZ, neural stem/progenitor cells (NSPCs) express the glial fibrillary acidic protein (GFAP) and selective depletion of these NSPCs drastically decreases cell proliferation in vitro and in vivo. In the hypothalamus, GFAP is expressed by α-tanycytes, which are specialized radial glia-like cells in the wall of the third ventricle also recognized as NSPCs. To explore the role of these hypothalamic GFAP-positive tanycytes, we used transgenic mice expressing herpes simplex virus thymidine kinase (HSV-Tk) under the control of the mouse Gfap promoter and a 4-week intracerebroventricular infusion of the antiviral agent ganciclovir (GCV) which kills dividing cells expressing Tk. While GCV significantly reduced the number and growth of hypothalamus-derived neurospheres from adult transgenic mice in vitro, it causes hypogonadotropic hypogonadism in vivo. The selective death of dividing tanycytes expressing GFAP indeed results in a marked decrease in testosterone levels and testicular weight, as well as vacuolization of the seminiferous tubules and loss of spermatogenesis. Additionally, GCV-treated GFAP-Tk mice show impaired sexual behavior, but no alteration in food intake or body weight. Our results also show that the selective depletion of GFAP-expressing tanycytes leads to a sharp decrease in the number of gonadotropin-releasing hormone (GnRH)-immunoreactive neurons and a blunted LH secretion. Overall, our data show that GFAP-expressing tanycytes play a central role in the regulation of male reproductive function.

Coenzyme Q10, oxidative stress, and male infertility: A review.

Male infertility has a complex etiopathology, which mostly remains elusive. Although research has claimed that oxidative stress (OS) is the most likely underlying mechanism of idiopathic male infertility, the specific treatment of OS-mediated male infertility requires further investigation. Coenzyme Q10 (CoQ10), a vitamin-like substance, has been found in measurable levels in human semen. It exhibits essential metabolic and antioxidant functions, as well as playing a vital role in mitochondrial bioenergetics. Thus, CoQ10 may be a key player in the maintenance of biological redox balance. CoQ10 concentrations in seminal plasma directly correlate with semen parameters, especially sperm count and sperm motility. Seminal CoQ10 concentrations have been shown to be altered in various male infertility states, such as varicocele, asthenozoospermia, and medical or surgical regimens used to treat male infertility. These observations imply that CoQ10 plays an important physiological role in the maintenance and amelioration of semen quality. The present article thereby aimed to review the possible mechanisms through which CoQ10 plays a role in the regulation of male reproductive function, and to concisely discuss its efficacy as an ameliorative agent in restoring semen parameters in male infertility, as well as its impact on OS markers, sperm DNA fragmentation, pregnancy, and assisted reproductive technology outcomes.

Leptin and inflammatory factors play a synergistic role in the regulation of reproduction in male mice through hypothalamic kisspeptin-mediated energy balance

BackgroundEnergy balance is closely related to reproductive function, wherein hypothalamic kisspeptin mediates regulation of the energy balance. However, the central mechanism of kisspeptin in the regulation of male reproductive function under different energy balance states is unclear. Here, high-fat diet (HFD) and exercise were used to change the energy balance to explore the role of leptin and inflammation in the regulation of kisspeptin and the hypothalamic-pituitary-testis (HPT) axis.MethodsFour-week-old male C57BL/6 J mice were randomly assigned to a normal control group (n = 16) or an HFD (n = 49) group. After 10 weeks of HFD feeding, obese mice were randomly divided into obesity control (n = 16), obesity moderate-load exercise (n = 16), or obesity high-load exercise (n = 17) groups. The obesity moderate-load exercise and obesity high-load exercise groups performed exercise (swimming) for 120 min/day and 120 min × 2 times/day (6 h interval), 5 days/week for 8 weeks, respectively.ResultsCompared to the mice in the normal group, in obese mice, the mRNA and protein expression of the leptin receptor, kiss, interleukin-10 (IL-10), and gonadotropin-releasing hormone (GnRH) decreased in the hypothalamus; serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone levels and sperm quality decreased; and serum leptin, estradiol, and tumor necrosis factor-α (TNF-α) levels and sperm apoptosis increased. Moderate- and high-load exercise effectively reduced body fat and serum leptin levels but had the opposite effects on the hypothalamus and serum IL-10 and TNF-α levels. Moderate-load exercise had anti-inflammatory effects accompanied by increased mRNA and protein expression of kiss and GnRH in the hypothalamus and increased serum FSH, LH, and testosterone levels and improved sperm quality. High-load exercise also promoted inflammation, with no significant effect on the mRNA and protein expression of kiss and GnRH in the hypothalamus, serum sex hormone level, or sperm quality. Moderate-load exercise improved leptin resistance and inflammation and reduced the inhibition of kisspeptin and the HPT axis in obese mice. The inflammatory response induced by high-load exercise may counteract the positive effect of improving leptin resistance on kisspeptin and HPT.ConclusionDuring changes in energy balance, leptin and inflammation jointly regulate kisspeptin expression on the HPT axis.

Thyroid hormones in male reproduction and infertility

Thyroid hormones have been well studied for its relevance to male reproduction in the last few decades. They are considered as essential regulators of male reproductive functions and play vital roles in male gonadal developments. Hyperthyroidism and hypothyroidism both affect testicular functions and influence neuroendocrine regulations over reproductive functions via the crosstalk between the hypothalamic-pituitary-thyroid axis and the hypothalamic-pituitary-gonadal axis. The alterations in the male reproductive hormonal milieu by thyroid hormones may lead to reduced testosterone levels and deterioration of semen quality. However, there are very few reports on the direct effects of thyroid disorders upon testicular functions and semen quality. This article aims to review the available literature to present a concise updated concept on the regulation of male reproductive functions by the thyroid hormones, and the possible mechanism by which thyroid dysfunctions affects testicular functions.

Orexins and male reproduction

Orexins (or hypocretins) are hypothalamic neuropeptides with a multitude of physiological functions. They occur in two known forms, namely, orexin A and orexin B with a common precursor, preproorexin. The orexin receptors (orexin 1R and orexin 2R) belong to the Family of G-protein coupled receptors. The primary function of the orexin system, i.e. the orexins, their receptors and associated neuronal circuitries, perhaps is to increase spontaneous physical activity and food intake, thereby promoting an increase in energy expenditure. Reports suggest that orexins may be the key brain components to mediate the mechanism of obesity resistance. Recent research also has thrown lights upon a significant role of orexins, especially orexin A, in regulation of male reproductive functions owing to their receptor expressions in vital testicular cells, such as Leydig cells, Sertoli cells as well as spermatozoa at different developmental stages, even in the epididymis and penis. Moreover, orexins have been reported to greatly influence gonadotropin-releasing hormone neurons and their secretions to regulate reproductive functions via modulation of the hypothalamic-pituitary-gonadal axis. Evidence thus implicates participation of orexins in steroidogenesis, spermatogenesis, transportation and maturation of sperm as well as in the control of penile function. However, further research is required in this direction to elucidate the mechanisms by which orexins play a role in different testicular functions and effect of orexins on semen quality.

Review of the role of leptin in the regulation of male reproductive function.

Since discovered in 1994, leptin has been thought to be a pleiotropic hormone that regulates food intake, controls energy balance in the body and influences multiple tissues in the body. Leptin plays an important mediating role in the regulation of neuroendocrine and can transmit the nutritional status signals to the reproductive-related central nervous system. Many studies have shown that leptin may play an important role in the control of reproductive function. Leptin can act on all levels of the hypothalamus-pituitary-gonadal (HPG) axis and may have local effects on the function of testis and spermatogenesis. Leptin is critical for puberty initiation and can also modulate testosterone synthesis by downregulating cAMP-dependent activation of steroidogenic genes expressions. Leptin is found to be higher in infertile men than in normal subjects. Yet, the exact role of leptin in the regulation of male reproductive function remains incomplete. The purpose of this review was to summarise the recent research about the biological effects of leptin on male reproductive system. In-depth study of leptin in reproductive system will help to reveal the pathogenesis of infertility and provide new treatment ideas for human assisted reproductive technology.

In situ hybridization and immunohistochemical localization of leptin hormone and leptin receptor in the seminal vesicle and prostate gland of adult rat

The role of leptin in the regulation of male reproductive function is still a matter of debate. Knowledge about a possible source of leptin in the seminal plasma may therefore be helpful in identifying and elucidating the physiological role of leptin hormone in male reproduction. In our investigation, the expression of leptin and its long receptor isoform (Ob-Rb) was studied in adult male Wistar rats using RT-PCR, Southern blot, in situ hybridization and immunohistochemistry. RT-PCR analysis revealed the expression of both leptin and its Ob-Rb in the seminal vesicle and prostate gland. In situ hybridization also localized the mRNA transcripts of leptin and Ob-Rb in the glandular secretory epithelial cells of prostate gland and seminal vesicle. Immunohistochemistry detected the leptin hormone in the lining epithelium of both male genital glands. In conclusion, these findings suggest that the seminal vesicle and prostate gland could be the possible sources of leptin in the seminal plasma. This leptin might have a direct (paracrine, autocrine or both) effect on epithelial cells of the accessory male genital glands, on the spermatozoa via spermatozoan leptin receptors.

PGF 2α, LH, testosterone, oestrone sulphate, and cortisol plasma concentrations around sexual stimulation in jackass

Many hormones are involved in the regulation of male reproductive functions, controlling sexual behavior, and influencing sexual arousal, the onset of erection and ejaculation, and the post-ejaculatory detumescence. The aims of this study were to analyze the plasma concentrations of 15-ketodihydro-PGF 2α (PGFM), LH, testosterone (T), oestrone sulphate (OS), and cortisol (C) in relation to sexual stimulation and to evaluate the possible correlations among circulating hormones and between hormones and semen characteristics in the donkey stallion. Thirteen sexually experienced Martina Franca jackass of proven fertility were enrolled and semen was collected through an artificial vagina. Plasma samples were collected at 12, 9, 6 and 3 min before oestrous jenny exposure, at the first erection in the mating arena in the presence of an oestrous jenny, during ejaculation, at dismounting, 3, 6, 9 and 12 min after ejaculation in box, and then every 10 min during the following 50 min. PGFM showed an increasing trend with significant differences between the pre-ejaculatory and post-ejaculatory period, suggesting a role of this hormone in the control of ejaculation. LH showed a significantly higher concentration at ejaculation compared to last samples, while T showed significantly higher levels at erection, ejaculation and dismounting, probably for its influence on these processes and on sexual behavior. Finally, OS did not show any difference in the period of observation, while C presented a significant increase only 22 minutes after erection. The only hormonal correlation found was a positive one between LH and T at erection and dismounting, while T and OS were positively correlated with total and progressive motility, respectively.

Effets des estrogènes sur le développement du testicule pendant la vie fœtale et néonatale

Estrogens are classically known to play a major role in female reproduction but there is now compelling evidence that they may also be involved in the regulation of male reproductive function. In humans, a decrease in sperm count and an increase in the incidences of testicular cancer, cryptorchidism and hypospadia have been observed in many countries over the last 50 years. Male reproductive alterations were also observed in wildlife. Such male reproductive disorders have been attributed to the increase in concentration of xenobiotics, and of xenoestrogens in particular, in the environment and in food. Epidemiological, clinical and experimental studies have suggested that excessive exposure to estrogens during fetal/neonatal life can lead to reproductive disorders in adulthood. Using an in vitro model we showed that estrogens directly affected the development of the fetal testis and we evidenced the existence of periods of sensitivity throughout development. Lastly, we clearly demonstrated that the fetal and neonatal testis is very sensitive to estrogens since the invalidation of estrogen receptor alpha leads to an increase of steroidogenesis and the invalidation of estrogen receptor beta enhances the development of the germ cell lineage in the male.

Le testicule fœtal est-il en danger ?

Estrogens are classically known to play a major role in female reproduction, but there is now compelling evidence that they may also be involved in the regulation of male reproductive function. In humans, a decrease in sperm count and an increase in the incidences of testicular cancer, cryptorchidism and hypospadia have been observed in many countries over the last 50 years. Male reproductive alterations were also observed in wildlife. Such male reproductive disorders have been attributed to the increase in concentration of xenobiotics, and of xenoestrogens in particular, in the environment and in food. Epidemiological, clinical and experimental studies have suggested that excessive exposure to estrogens during fetal/neonatal life can lead to reproductive disorders in adulthood. Using an in vitro model, we showed that estrogens directly affected the development of the fetal testis. Lastly, we clearly demonstrated that the fetal and neonatal testis is very sensitive to estrogens since the invalidation of estrogen receptor alpha leads to an increase of steroidogenesis and the invalidation of estrogen receptor beta enhances the development of the germ cell lineage in the male.

Aromatase expression in male germ cells

The cytochrome P450 aromatase (P450arom) is the terminal enzyme responsible for the formation of estrogens from androgens. According to the age, aromatase activity has been measured in immature and mature rat Leydig cells, as well as in Sertoli cells whereas in pig, ram and human the aromatase is mainly present in Leydig cells. In the rat testis, we have immunolocalised the P450arom not only in Leydig cells but also in germ cells and especially in elongated spermatids. Related to the stage of germ cell maturation, we have shown that the level of P450arom mRNA transcripts decreases, it is much more abundant in younger than in mature germ cells whereas the aromatase activity is two- to four-fold greater in spermatozoa when compared to the two other enriched-germ cell preparations. Moreover, we have reported the existence of alternative splicing events of P450arom mRNA in pachytene spermatocytes and round spermatids giving rise to two isoforms lacking the last coding exon which, therefore, cannot encode functional aromatase molecules. In rat germ cells, the aromatase gene expression is not only under androgen control but also subjected to cytokine (TNFα) and growth factor (TGFβ) regulation. In the bank-vole testis, we have evidenced a synchronisation between a fully developed spermatogenesis and a strong positive immunoreactivity for both P450arom and estrogen receptor (ERβ) in spermatids. Therefore, the aromatase gene expression and its translation in a fully active protein in rodent germ cells evidence an additional site for estrogen production within the testis. Our recent data showing that human ejaculated spermatozoa expressed specific transcripts for P450arom reinforced the observations reported in germ cells of other mammalian species. Together with the widespread distribution of ERs in testicular cells these data bring enlightenments on the hormonal regulation of male reproductive function. Indeed these female hormones (or the ratio androgens/estrogens) do play a physiological role (either directly on germ cells or via testicular somatic cells) in the maintenance of male gonadal functions and obviously, several steps are concerned particularly the spermatid production and the epididymal sperm maturation.

Testicular Estrogens and Male Reproduction.

Besides somatic cells, aromatase gene expression and its transduction in an active protein in germ cells provides evidence of an additional site for estrogen production within testes of some mammals. Together with the widespread distribution of estrogen receptors in testicular cells, these data illuminate the hormonal regulation of male reproductive function

Role of FSH in the regulation of spermatogenesis: clinical aspects.

IntroductionUnder normal conditions male reproduction in mammalsrequires four distinct components which have to interact in aconcerted fashion with female reproductive functions toguarantee successful procreation:•sperm as the actual carrier of genetic information and as thefertilizing agent;•semen as the transport medium for sperm;•organs to transfer semen into the female genital tract;•male sexual behaviour.In addition to genetic, neuronal and vascular integrity hormonesare essential for the regular function of the four components. Inparticular, the endocrine feedback-mechanism involvinghypothalamus, pituitary and testis is responsible for eachcomponent and their coordinated interplay. One hypothalamichormone, GnRH, is responsible for the release of twogonadotrophins, FSH and LH, and the exact role of the twogonadotrophins in male reproduction remains an enigma ofandrological research.Through mediation by specific receptors both gonadotro-phins act on the testis: LH on Leydig cells and FSH on Sertolicells, and it is unclear why the single hypothalamic signal istranslated into a dual pituitary signal controlling malereproductive functions. The early concept of regulation oftesticular function surmised that LH stimulates testosteroneproduction and FSH controls spermatogenesis (Greep, 1937).However, so far only one mammalian animal model could bediscovered where such a clear separation of the two functionsmay occur, i.e. the Djungarian hamster. In this seasonal breederFSH can induce full spermatogenesis and viable sperm(function 1 above) while testosterone appears to be requiredonly for functions 2–4 (Lerchl et al., 1993; Niklowitz et al.,1997). In most other mammals, in particular, in nonhuman andhuman primates the roles played by the two gonadotrophins inthe regulation of male reproductive functions appear to be muchmore closely interwoven. However, recent findings in geneti-cally manipulated mice have suggested that FSH may not berequired for spermatogenesis (e.g. Kumar et al., 1997; Dierichet al., 1998). Although extrapolating data from small laboratoryrodents to the humans has its limitations, these findings haveleft many clinicians in a quandary concerning the role of FSH inhuman spermatogenesis and its implications for diagnosis andtreatment of male hypogonadism and infertility.The purpose of this brief review is to summarize the currentknowledge about the role of FSH as distinct from that of LH andtestosterone in human male reproduction. Experimentalevidence from nonhuman primates as the most relevantanimal model is used to substantiate findings in humans.Since initiation of spermatogenesis may have differenthormonal requirements than maintenance of the process, thetwo situations are considered separately. Moreover, a distinc-tion between qualitatively and quantitatively normal sperma-togenesis will be drawn. The evidence cited for a role of FSHalone or LH/testosterone alone or for synergism of the twogonadotrophins is summarized in Tables 1 and 2.Role of FSH in the initiation of spermatogenesisPatients with hypogonadotrophic hypogonadism represent avaluable experimental model to study the role of gonado-trophins in spermatogenesis. Patients with secondaryhypogonadism due either to idiopathic hypogonadotrophichypogonadism (IHH) and Kallmann’s syndrome or to hypo-pituitarism can be effectively treated with pulsatile GnRH or acombination of both gonadotrophins in order to inducespermatogenesis and achieve fertility (Whitcomb & Crowley,1990; Burgues et al., 1997; Bu¨chter et al., 1998). Under thesetreatments sperm appear in the ejaculate and sperm concentra-tions increase progressively. However, sperm concentrationsreach normal values in only few patients, although this is notnecessary for the induction of pregnancy, and the time requiredto achieve a pregnancy can be quite variable (Bu¨chter et al.,1998).Under clinical conditions it appears that both gonadotro-phins, either stimulated by GnRH or given directly, are requiredto achieve fertility in such patients while FSH alone or incombination with low-dose testosterone is not able to inducefertility (Schaison et al., 1993). This failure of FSH treatmentto induce spermatogenesis in hypogonadotrophic patientscontrasts with the observation of the fertile eunuch syndrome,

Sources of oestrogen in the testis and reproductive tract of the male.

The cytochrome P450 aromatase (P450arom) is the terminal enzyme responsible for the irreversible transformation of androgens into oestrogens and is present in the endoplasmic reticulum of various tissues throughout at least the phylum of vertebrates. The CYP 19 gene is unique and its expression is regulated in a tissue and more precisely in a cell-specific fashion via the alternative use of several promoters located in the first exons. The P450arom has been immunolocalized in germ cells of the mouse, brown bear and rooster. According to age, aromatase activity has been measured in immature and mature rat Leydig cells as well as in Sertoli cells, whereas in the pig, ram and human aromatase is mainly present in Leydig cells. In the adult rat testis, four complementary approaches (RTPCR, in situ hybridization, immunocytochemistry and the tritiated water assay) demonstrate that not only somatic cells but also mature germ cells represent a source of oestrogen synthesis. Taking into account the widespread distribution of oestrogen receptors (ER alpha & ER beta) in testicular cells and the genital tract of the male on the one hand, and the cross-talk between sex steroids and growth factors, and between membrane receptors and nuclear receptors for steroids on the other hand, it is anticipated that understanding of the pathophysiological roles of these 'female' hormones in the male will advance understanding of the hormonal regulation of male reproductive function. One of the future goals is to define oestrogen-targeted genes in the male gonad and indeed, a lot of work is now focused on this specific area in order to clarify the role of oestrogens in the reproductive tract of the male as well as to elucidate the regulation of aromatase gene expression.

The Role of Growth Hormone and Insulin-Like Growth Factor I in the Regulation of Male Reproductive Function

Animal experiments and clinical studies on the interactions between growth hormone (GH) and the male hypothalamic-pituitary-gonadal axis have predominantly concentrated on GH and sex steroid interactions in the regulation of growth and development, or on the metabolic effects of GH. In contrast, little attention has been paid to the possible effects of GH on spermatogenesis, although the first report dealing with this topic was published almost 30 years ago. The interactions of GH and its main mediator, insulin-like growth factor I (IGF-I), with the hypothalamic-pituitary-gonadal axis, and their role in spermatogenesis have recently been investigated using in vitro systems and different animal models (mice and rats). Using Leydig and Sertoli cell cultures, complex interactions between GH/IGF-I and the gonadotropins affecting differentiated cell functions, e.g. steroidogenesis and cell division, have been demonstrated at the cellular level. In vivo studies using immature and mature hypophysectomized rats and GH-deficient mutant male mice and rats indicate that IGF-I can play an important role in the regulation of steroidogenesis and spermatogenesis. Furthermore, although follicle-stimulating hormone and luteinizing hormone are the major regulators of testicular IGF-I production, GH may play an indirect role by potentiating the actions of the gonadotropins in regulating testicular IGF-I content. A large proportion of men presenting at male-infertility clinics are diagnosed as having idiopathic infertility. Further studies are necessary to investigate whether defects associated with GH and/or IGF-I effects in the testis are the cause of male infertility in a small group of these patients.