Endocrinology of The Male and Spermatogenesis PDF

Lecture 15 Endocrinology of the male and spermatogenesis AGSC310 –Physiology of Reproduction Luis Fernando Schutz, Ph.D. 1  Spermatogenesis Learning objectives: Ø Know the cells that support ster...

Lecture 15 Endocrinology of the male and spermatogenesis AGSC310 –Physiology of Reproduction Luis Fernando Schutz, Ph.D. 1  Spermatogenesis Learning objectives: Ø Know the cells that support steroidogenesis Ø Understand the endocrine regulation of spermatogenesis Ø Understand the three phases of spermatogenesis 2  Spermatogenesis Spermatozoon produced in the seminiferous tubules in a process called billions are produced every day spermatogenesis released continually from the production is supported by seminiferous epithelium Sertoli and Leydig cells 3  Endocrinology Cells that support spermatogenesis Ø the parenchyma of the testis is made up of seminiferous tubules and interstitial tissue: v Sertoli cells are located in the seminiferous tubules v Leydig cells are located in the interstitial tissue close to seminiferous produce tubules so there's a lot testosterone of communication between them 4  Endocrinology Cells that support spermatogenesis Ø Sertoli cells: v are the male equivalent to the follicular granulosa cells and their functions depend on FSH v produce several substances to support spermatogenesis v regulates the production of testosterone Ø Leydig cells: v are the male equivalent to the theca interna and bind to LH v produce testosterone 5  Endocrinology Cells that support spermatogenesis Ø Sertoli cells: support spermatogenesis v produce several substances to support spermatogenesis: 1) androgen binding protein (ABG): testosterone binding protein ü concentrates testosterone in the seminiferous tubules, which supports spermatogenesis 2) sulfated glycoproteins (SGP) 1 and 2: ü SGP-1: related to fertility acquisition ü SGP-2: provides a detergent effect for sperm and fluid to move through the testis 3) transferrin: ü an iron-transport protein required for successful spermatogenesis 6  Endocrinology Cells that support spermatogenesis Ø Sertoli cells: v regulates the production of testosterone (does not produce it) ü bind to FSH easttss.tnatffYstosfer8Te1Gaetan good amountifosterone ü convert testosterone produced by the Leydig cells into estradiol, which results in the suppression of GnRH release by the hypothalamus § the suppression of GnRH release by estradiol prevents a continuous LH release, which will be released in a pulsatile manner ü produce inhibin, which will inhibit FSH production by the anterior pituitary 7  Endocrinology Cells that support spermatogenesis Ø Leydig cells: produce testosterone v synthesize testosterone in response to LH ü Leydig cells bind to LH, produce progesterone, and convert progesterone into testosterone 8  Endocrinology Cells that support spermatogenesis Ø Leydig cells: v the response of Leydig cells to LH is short and the secretion of testosterone is pulsatile, lasting for a period of about 20 min to 60 min ü testosterone synthesis is pulsatile because LH secretion is pulsatile ü a pulsatile LH secretion maintain adequate testosterone levels § if LH would be constant, Leydig cells would stop responding to LH by decreasing its numbers of available LH receptors – this would result in reduced secretion of testosterone if comes binds to receptors then goes stops for awhile § if LH secretion would be long, Leydig cells would secrete testosterone for hours rather than minutes and testosterone would exert a sustained negative feedback on GnRH release by hypothalamus - this would result in reduced secretion of testosterone too much or too little isn't good FILIATION CAN 9 9  Endocrinology Cells that support spermatogenesis Ø Leydig cells: v testosterone is critically important for spermatogenesis v testosterone supports: ü the completion of meiosis of sperm cells Testosterone ü the adhesion of elongated spermatids to Sertoli cells ü the release of sperm from seminiferous tubules 10  Endocrinology Endocrine control of spermatogenesis Ø Before spermatozoa can be produced, the following endocrine requirements must be met: 1) adequate secretion of GnRH 2) FSH and LH secretion from the anterior pituitary 3) secretion of steroids (testosterone and estradiol) Importanttoalievepuberty 11 always fertile  Endocrinology Endocrine control of spermatogenesis Ø secretion of GnRH and gonadotropins v the hypothalamus in the male does not develop a surge center, so the tonic center is the main responsible to release GnRH constant TO they don't have surge center only tonic center v ecretion in the main source of progesterone in the female is the corpus me female luteum, so progesterone levels will be much lower in the male than in the female ü progesterone will not prevent the tonic center to release GnRH, so discharges of high amplitude of GnRH and gonadotropins are much more frequent in the male than in the female more frequent in the male 12  Endocrinology Endocrine control of spermatogenesis Ø secretion of GnRH and gonadotropins v the discharge of GnRH from the hypothalamus occurs in frequent and intermittent episodes ü this frequency of GnRH release in the male is very different than in the female, when a high amplitude GnRH pulse is released only in a preovulatory surge because of the negative feedback of progesterone ü the bursts of GnRH in the male last only for a few minutes and cause discharges of FSH and LH following almost immediately GnRH ü the episodes of LH last from 10 to 20 minutes and occur between 4 to 8 times every 24 h 13  Endocrinology Endocrine control of spermatogenesis Ø secretion of GnRH and gonadotropins v the pulses of FSH last 100 minutes and occur between 4 to 8 times every 24 h v concentrations of FSH are lower, but the pulses are of longer duration than LH because of the following: ü inhibin production by the adult testis is relatively constant ü FSH has a longer half-life than LH 14  Endocrinology Differences in LH between male and female Ø LH in male: Ø LH in female: v GnRH released by the tonic center v GnRH released by the tonic center of hypothalamus stimulate the of hypothalamus stimulate basal release of LH levels of LH v the pulsatile LH bind to Leydig v basal levels of LH bind to theca cells cells to produce testosterone to produce testosterone throughout folliculogenesis v episodes of LH last from 10 to 20 minutes and occur between 4 to 8 119s v the preovulatory surge of LH: statedp of LH times every 24 h ü responds to GnRH from the surge center ü there is no surge center of and is regulated by progesterone hypothalamus ü promotes final growth and maturation of ü progesterone does not regulate GnRH dominant follicles and ovulation release 15  Endocrinology Differences in LH between male and female P4 E2 LH FSH Metestrus Diestrus Proestrus Estrus 0 3 6 9 12 15 h 0 15 hours 0 21 days v high-amplitude episodes of GnRH, FSH, and Ø the interval between high amplitude LH surges is LH occur between 4 to 8 times every 24 h several days v in response to LH, testosterone is released in a Ø progesterone prevents the release of high pulsatile manner that is constant throughout the amplitude LH until the dominant follicle(s) is days ready to maturate and ovulate 16 doesn't have a ohas male a cycle oestrodial is important for the cycle estrus behavior for COPULATION  Endocrinology Discussion time! Ø in groups of 3-4, discuss: v explain functions of Sertoli and Leydig cells Sertoli cells regulate testosterone Leydig cells producetestosterone v how do gonadotropins regulate Sertoli and Leydig cells functions v discuss functions of testosterone S 8 EEn.SEfTneioEmioefrsima v how is the regulation of GnRH and gonadotropins release in the male? what is the role of estradiol produced by Sertoli cells? 17  Spermatogenesis Spermatogenesis Ø is the process of producing spermatozoa Ø takes place in the seminiferous tubules Ø consists of cell divisions and morphologic changes of developing germ cells Ø can be subdivided into three phases: 1. proliferation phase 2. meiotic phase 3. differentiation phase 18  Spermatogenesis Spermatogenesis 1. proliferation phase Ø consists of all mitotic divisions of spermatogonia v spermatogonia: ü fingeratous are the most primitive cells encountered in the seminiferous epithelium ü are specialized diploid cells (2N chromosomal content) ü are located in the basal compartment of the seminiferous epithelium ü there are 3 types of spermatogonia: § A-spermatogonia § § I-spermatogonia (intermediate) B-spermatogonia 2 19  Spermatogenesis Spermatogenesis 1. proliferation phase Ø several generations of A-spermatogonia undergo mitotic divisions, generating a large number of B-spermatogonia v A-spermatogonia undergo several mitotic divisions in which they progress mitotically from A1 through A4 v mitotic divisions of spermatogonia A4 will result in I-spermatogonia v mitotic divisions of I-spermatogonia will result in B-spermatogonia v finally, mitotic divisions of B-spermatogonia will result in the formation of primary spermatocytes 20  Spermatogenesis Spermatogenesis 1. proliferation phase v an important part of the proliferation phase is stem cell renewal ü loss of intercellular bridges allows some spermatogonia to revert to stem cells (spermatogonial stem cells) providing continual renewal of these stem cells from which new spermatogonia can develop stench is why they v a pool of stem cells is maintained so that spermatogenesis can always have continue indefinitely sperm ü stem cells divide mitotically to provide a continual source of A- fertili spermatogonia, allowing spermatogenesis to continue without interruption for years 21  Spermatogenesis Spermatogenesis 2. meiotic phase Ø begins with primary spermatocytes Ø during meiosis I, genetic diversity is guaranteed by DNA 00 replication and crossing over during the production of 0 secondary spermatocytes v from a genetic perspective, each sperm is different than the others Ø the conclusion of the meiotic phase is the meiosis II: v secondary spermatocytes will become spermatids 22 they become spermatids  Spermatogenesis Spermatogenesis 2. meiotic phase Ø meiotic divisions produce 4 haploid (1N chromosomal content) spermatids during the meiotic phase of spermatogenesis v each primary spermatocyte will give rise to 4 spermatids ü each primary spermatocyte gives rise to 2 secondary spermatocytes ü each secondary spermatocyte gives rise to 2 spermatids 23  Spermatogenesis Spermatogenesis 3. differentiation phase Ø no further cell divisions occur Ø this phase is commonly called “spermiogenesis” v during this phase, a spherical undifferentiated spermatid undergoes a transformation that results in the production of a fully differentiated, highly specialized spermatozoon containing: ü a head (nuclear material) of the o each ü a flagellum including a midpiece (with a mitochondrial helix) sperm has each of ü a principal piece these parts 24  Spermatogenesis Spermatogenesis Ø the most immature germ cells (spermatogonia) are located at the periphery of a seminiferous tubule near the basement membrane they get v as these germ cells proliferate, they move toward the lumen released v developing germ cells are connected by intercellular bridges from ü groups of spermatogonia, spermatocytes or spermatids are connected by intracellular bridges, so that the cytoplasm of each group of cells of the same type is interconnected ü the intercellular bridges provide communication between cells that contributes to synchronized development of a cohort (group of cells) 25  Spermatogenesis Spermatogenesis the most immature germ cells are located at the periphery of a seminiferous tubule near the basement membrane as the spermatogonia proliferate, they move toward the lumen meiosis and differentiation occur in the adluminal compartment of the seminiferous tubule each generation of cells is attached by intercellular cytoplasmic bridges, which divides the generations into cohorts 26