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The NR4A1 gene is a transcription factor important in the development of cells that secrete the hormone insulin-like 3 (INSL3). In general, the NR4A gene family regulates cell growth and differentiation.
In humans, INSL3 aids in the regulation of testicular descent during fetal development. In an adult INSL3 helps in keeping germ cells alive, in both males and females.
In the male reproductive system the NR4A1 gene is a promoter of insulin-like 3 in Leydig cells. Leydig cells are located in the testis and known for the function as a support cell in spermatogenesis. Along with other things they secrete testosterone.
In females, INSL3 is also involved in the reproductive system. It is secreted by thecal and luteal cells in the ovary and thus is important in the maturation of developing oocytes. In the rabbit model, disorders observed involving NR4A1 expression include testicular dysgenesis, and cryptorchidism.
Immunoprecipitation assays show that INSL3 does bind to NR4A1; however, much is still not known about INSL3 regulation and the direct involvement of the NR4A1 gene.
The endocrine system is a messenger system comprising feedback loops of the hormones released by internal glands of an organism directly into the circulatory system, regulating distant target organs. In vertebrates, the hypothalamus is the neural control center for all endocrine systems. In humans, the major endocrine glands are the thyroid gland, parathyroid gland, pituitary gland, pineal gland, the testes (male), ovaries (female), and the adrenal glands. The hypothalamus, pancreas, and thymus also function as endocrine glands, among other functions. Other organs, such as the kidneys, also have roles within the endocrine system by secreting certain hormones. The study of the endocrine system and its disorders is known as endocrinology. It is one of the most important systems of the human body.
A gonad,sex gland, or reproductive gland is a mixed gland that produces the gametes and sex hormones of an organism. Female reproductive cells are egg cells, and male reproductive cells are sperm. The male gonad, the testicle, produces sperm in the form of spermatozoa. The female gonad, the ovary, produces egg cells. Both of these gametes are haploid cells. Some hermaphroditic animals have a type of gonad called an ovotestis.
Spermatogenesis is the process by which haploid spermatozoa develop from germ cells in the seminiferous tubules of the testis. This process starts with the mitotic division of the stem cells located close to the basement membrane of the tubules. These cells are called spermatogonial stem cells. The mitotic division of these produces two types of cells. Type A cells replenish the stem cells, and type B cells differentiate into primary spermatocytes. The primary spermatocyte divides meiotically into two secondary spermatocytes; each secondary spermatocyte divides into two equal haploid spermatids by Meiosis II. The spermatids are transformed into spermatozoa (sperm) by the process of spermiogenesis. These develop into mature spermatozoa, also known as sperm cells. Thus, the primary spermatocyte gives rise to two cells, the secondary spermatocytes, and the two secondary spermatocytes by their subdivision produce four spermatozoa and four haploid cells.
Sertoli cells are a type of sustentacular "nurse" cell found in human testes which contribute to the process of spermatogenesis as a structural component of the seminiferous tubules. They are activated by follicle-stimulating hormone (FSH) secreted by the adenohypophysis and express FSH receptor on their membranes.
Relaxin is a protein hormone of about 6000 Da, first described in 1926 by Frederick Hisaw.
The steroidogenic factor 1 (SF-1) protein is a transcription factor involved in sex determination by controlling the activity of genes related to the reproductive glands or gonads and adrenal glands. This protein is encoded by the NR5A1 gene, a member of the nuclear receptor subfamily, located on the long arm of chromosome 9 at position 33.3. It was originally identified as a regulator of genes encoding cytochrome P450 steroid hydroxylases, however, further roles in endocrine function have since been discovered.
An ovotestis is a gonad with both testicular and ovarian aspects. In humans, ovotestes are an infrequent anatomical variation associated with gonadal dysgenesis. The only mammals where ovotestes are not symptomatic of an intersex variation are moles, wherein females possess ovotestes along with a masculinized clitoris. These ovotestes in nonpregnant female moles secrete eight times as much testosterone as the ovotestes of pregnant moles. In invertebrates that are normally hermaphroditic, such as most gastropods in the clade Eupulmonata, an ovotestis is a common feature of the reproductive anatomy.
Insulin-like growth factor-binding protein 4 is a protein that in humans is encoded by the IGFBP4 gene.
Relaxin/insulin-like family peptide receptor 2, also known as RXFP2, is a human G-protein coupled receptor.
Insulin-like 3 is a protein that in humans is encoded by the INSL3 gene.
Nuclear autoantigenic sperm protein is a protein that in humans is encoded by the NASP gene. Multiple isoforms are encoded by transcript variants of this gene.
Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A is an enzyme that in humans is encoded by the PDE1A gene.
Testicular Immunology is the study of the immune system within the testis. It includes an investigation of the effects of infection, inflammation and immune factors on testicular function. Two unique characteristics of testicular immunology are evident: (1) the testis is described as an immunologically privileged site, where suppression of immune responses occurs; and, (2) some factors which normally lead to inflammation are present at high levels in the testis, where they regulate the development of sperm instead of promoting inflammation.
Early placenta insulin-like peptide is a protein that in humans is encoded by the INSL4 gene.
Sperm protein associated with the nucleus on the X chromosome A is a protein that in humans is encoded by the SPANXA1 gene.
Inhibin, beta B, also known as INHBB, is a protein which in humans is encoded by the INHBB gene. INHBB is a subunit of both activin and inhibin, two closely related glycoproteins with opposing biological effects.
Gonocytes are the precursors of spermatogonia that differentiate in the testis from primordial germ cells around week 7 of embryonic development and exist up until the postnatal period, when they become spermatogonia. Despite some uses of the term to refer to the precursors of oogonia, it was generally restricted to male germ cells. Germ cells operate as vehicles of inheritance by transferring genetic and epigenetic information from one generation to the next. Male fertility is centered around continual spermatogonia which is dependent upon a high stem cell population. Thus, the function and quality of a differentiated sperm cell is dependent upon the capacity of its originating spermatogonial stem cell (SSC).
The insulin/IGF/relaxin family is a group of evolutionary related proteins which possess a variety of hormonal activities. Family members in human include two subfamilies:
Relaxin family peptide hormones in humans are represented by seven members: three relaxin-like (RLN) and four insulin-like (INSL) peptides: RLN1, RLN2, RNL3, INSL3, INSL4, INSL5, INSL6. This subdivision into two classes is based primarily on early findings, and does not reflect the evolutionary origins or physiological differences between peptides. For example, it is known that the genes coding for RLN3 and INSL5 arose from one ancestral gene, and INSL3 shares origin with RLN2 and its multiple duplicates: RLN1, INSL4, INSL6.
The fetal endocrine system is one of the first systems to develop during prenatal development of a human individual.
Luc J. Martin and Jacques J. Tremblay Nuclear Receptors in Leydig Cell Gene Expression and Function Biol Reprod July 2010 83 (1) 3–14; published ahead of print April 7, 2010, doi:10.1095/biolreprod.110.083824
Nicholas M. Robert, Luc J. Martin, and Jacques J. Tremblay The Orphan Nuclear Receptor NR4A1 Regulates Insulin-Like 3 Gene Transcription in Leydig Cells Biol Reprod February 2006 74 (2) 322–330; published ahead of print October 19, 2005, doi:10.1095/biolreprod.105.044560