Segabinazzi 2 - VetPrep - Reproductive endocrine control-3.pdf

Endocrine control of reproduction L. Segabinazzi 2024 DIESTRUS Goals Brief reminder about hormones Chemical nature Mechanism of action Understand feedbacks Understand supraphysiological stimulation “downregulation” Mechanism that triggers puberty Estrous cycle in mammal females Endocrine control - f...

Endocrine control of reproduction L. Segabinazzi 2024 DIESTRUS Goals Brief reminder about hormones Chemical nature Mechanism of action Understand feedbacks Understand supraphysiological stimulation “downregulation” Mechanism that triggers puberty Estrous cycle in mammal females Endocrine control - follicular growth, ovulation, luteinization, luteolysis Male endocrine control Vet Prep MM Gametogenesis Absence of ✔ Testis determining factor ✔ AMH ✔ Testosterone Most mammals are born with oogenesis at the beginning of Meiosis I – Primary oocyte Oocytes get arrested until puberty in prophase I (2N & 4C) Vet Prep MM ✔ Testis determining factor ✔ AMH ✔ Testosterone Differentiate to spermatogonium and multiply by mitosis Diploid cells (2N). Male mammals are born with spermatogonium that can undergo multiple mitosis Puberty The acquisition of reproductive competence Production of gametes Mating behavior What mediates puberty? Hypothalamus maturation – GnRH secretion/synthesis Onset of cyclicity in females Mature sperm in males Vet Prep MM Hormones Chemical messengers Most hormones are: Secreted by an endocrine gland Carried by the bloodstream Affect other organs, glands, or tissues. Controls metabolic processes Signaling molecules produced in the body that regulate the activity of certain cells and organs VetPrep MM Classification of hormones Chemical nature Steroid Derived from cholesterol Androgens Metabolized in the liver (firstpass) Ex.: Estrogens, testosterone, progesterone Amine hormones The amino acid-derived hormones are relatively small molecules that are derived from the amino acid tyrosine and tryptophan. Easily metabolized Name of amino acidderived ends in “-ine” Ex.: Dopamine, Epinephrine Physiology MM II - Reproduction Stomach enzymatic degradation Eicosanoids Protein/peptide Larger proteins or small/medium size peptides (chain of amino acids) Much larger than steroids and amine hormones Water-soluble – membrane receptors Short peptides – Ex.: oxytocin Small proteins – Ex.: growth hormones Glycoproteins – Ex.: FSH, LH FSH Derived from polyunsaturated fatty acids from the cell membrane usually arachidonic acid (20-carbon) Key mediators and regulators of inflammation and immunity Paracrine Ex.: Prostaglandins Classification of hormones VetPrep MM Mechanism of action Bind to cell membrane receptors Bind to intracellular receptors Form hormone-receptor (H-R) complexes Biochemical function mediated by H-R complex Lipophilic Found in the circulation in association with transport proteins Longer half-life (hours or days) Ex.: Steroids Hormones bind the cell membrane receptors (Gprotein), which induce the release of secondary messengers. Secondary messengers perform the biochemical function. Hydrophilic Transported in the free-form Short Half-life (minutes) Ex.: Amino acid derived and eicosanoids Hormones Hormone control: Negative or Positive feedback Most endocrine hormones are regulated by negative feedback loops. Negative feedback keeps the concentration of a hormone within a relatively narrow range and maintains homeostasis. Ex.: Testosterone is essential for spermatogenesis. However, excessive concentrations of testosterone cause negative feedback on the anterior pituitary for the release of LH, which will consequently reduce the activity of Leydig cells for the production of testosterone. Very few endocrine hormones are regulated by positive feedback loops. Positive feedback causes the concentration of a hormone to become increasingly higher. Ex.: Estradiol produced by the pre-ovulatory follicle causes positive feedback to the Surge center of the hypothalamus, which will lead to the release of LH by the anterior pituitary. The LH will induce the ovulation of the pre-ovulatory follicle. VetPrep MM Hormones VetPrep MM Supraphysiological stimulation Exceeding what is normally found in healthy individuals Hormone becomes ineffective after long-term use “Internalization” of hormone receptors Once the peptide hormones are bound to their receptors on the appropriate target cells, they are internalized and degraded by the process of receptor-mediated endocytosis Ex.: Prolonged-release, high dose GnRH Used as a contraceptive in dogs and horses Physiologically, GnRH is responsible for follicular growth and ovulation Hormones Source of production Pineal gland: Melatonin Hypothalamus: GnRH, oxytocin Females: Surge and tonic centers Males: only tonic center VetPrep MM Hypothalamic-pituitary-gonadal axis Pituitary Gland: FSH, LH, Oxytocin release (posterior pituitary) Gonads: Ovary: Follicles - Estradiol, Inhibin; Corpus luteum - Progesterone, Oxytocin Testis: Testosterone, Inhibin, Estradiol Uterus: Prostaglandin F2 alpha Female estrous cycle Period from the beginning of one estrus to the beginning of the next (or from one ovulation to the next) P h y s i o l o g y I IMM - Reproduction Follicular phase - estrus (Proliferative phase in women) - estrogen Luteal phase - diestrus (Secretory phase in women) - progesterone Quiescent phase – anestrus – no hormones Estrus is defined behaviorally Female estrous cycle Hypothalamus Tonic GnRH Center Frequency of GnRH pulses controlled by a pulse generator Affected by internal and external signals Surge Center Responsible for bursts of GnRH required to achieve preovulatory LH surge Paraventricular nucleus Oxytocin synthesis – released by the posterior pituitary Portal system – delivery system: axons/neurons extend to blood vessels of the portal system GnRH affects the anterior pituitary directly Oxytocin is transported along the axons P h y s i o l o g y I IMM - Reproduction Surge Tonic Female estrous cycle Pituitary gland / Hypophysis Anterior pituitary or Adeno hypophysis Continuously produces FSH Preovulatory LH surge induced by the burst of GnRH from the Hypothalamic Surge center Affected by inhibin (negative feedback) Affected by Estradiol (positive feedback on the hypothalamic surge center) Posterior pituitary or Neuro hypophysis Responsible for storage and release of the oxytocin produced by the hypothalamus P h y s i o l o g y I IMM - Reproduction Female estrous cycle Ovary Medulla (intern) Vasculature, nerves, connective tissue Cortex (extern) Oocytes, Follicles, CL VetPrep MM Folliculogenesis “Resting pool” Pool of inactive primordial follicles Dormant phase (Prophase I) Committed follicle (four possibilities) Remains quiescent Die Begging development and atresia later Develop and ovulate Follicle activation is irreversible Unknown what triggers the primordial follicle activation Finite nest Intraovarian signaling – oocyte or granulosa cells Gonadotropin-independent growth Follicular development up to the formation of the antrum is independent of FSH or LH P h y s i o l o g y I IMM - Reproduction Gonadotropin dependent FSH LH Female estrous cycle P h y s i o l o g y I IMM - Reproduction Follicular dynamics Follicular growth occurs in waves or cohorts Number varies between and within species Recruitment CL Selection CL CL CL Dominance CL Atresia CL Ovulation Scarramuzzi et al., 2011, Reprod. Fertil. Devel Female estrous cycle Pineal gland: Melatonin Hypothalamus: GnRH Pituitary Gland: FSH, LH Ovary: P h y s i o l o g y I IMM - Reproduction Follicles - Estradiol, Inhibin, Testosterone; DIESTRUS Corpus luteum - Progesterone, Relaxin, Oxytocin C L Uterus: Prostaglandin F2 alpha C L C L CL CL Ovulation Scarramuzzi et al., 2011, Reprod. Fertil. Devel Female estrous cycle P h y s i o l o g y I IMM - Reproduction Follicles Primordial follicle Oocyte surrounded by a single layer of squamous cells Primary follicle Oocyte surrounded by a single layer of cuboidal cells Secondary follicle Oocyte surrounded by two or more layers Zona pellucida Antral follicle – completed Meiosis I Fluid accumulates within a cavity formed by follicular cells Female estrous cycle Antral Follicle Gonadotropin-dependent Theca externa Connective tissue Theca interna Produce androgens under LH stimulation Granulosa cells Produce Estrogen, Inhibin and follicular fluid Responsive to FSH P h y s i o l o g y I IMM - Reproduction Follicular deviation P h y s i o l o g y I IMM - Reproduction Inhibin Downregulation of FSH secretion Dominant follicle keeps developing because it has enough/more receptors for FSH Produces estradiol Subordinate follicles regress Induces synthesis of LH Induces ovulation Female estrous cycle Other ovarian structures Corpus hemorrhagicum (CH) Structure left immediately after ovulation Antrum collapses and is filled with blood Corpus luteum (CL) Theca interna and granulosa cells proliferate to fill the cavity, differentiate into luteal cells and produce Progesterone Large luteal cells (from granulosa; also secrete Oxytocin and Relaxin) Small luteal cells (from theca interna) Corpus albicans Remnant of old corpus luteum P h y s i o l o g y I IMM - Reproduction Female estrous cycle P h y s i o l o g y I IMM - Reproduction Follicles Non-pregnant Produces progesterone Produces estradiol FSH release is not affected. 1° CL Follicular growth ~Day 14 Secretion of oxytocin New estrus phase PGF2α causes luteolysis of the CL Around Day 1417 after ovulation Estradiol “Open” receptors of Oxytocin in the endometrium Endometrium produces PGF2α by the stimulation of oxytocin IF Non-maternal recognition of pregnancy Male fertility requires Competent spermatogenesis Endocrine regulation Thermoregulation Spermatogenesis Functional delivery system Accessory glands Erection, ejaculation Libido VetPrep MM Male Endocrinology of Male Reproduction Anti-Mullerian Hormone (AMH) – low concentrations in postnatal males Gonadotropin-releasing hormone (GnRH) Luteinizing hormone (LH) – induce T4 secretion by Leydig cells Follicle-stimulating hormone (FSH) – important for Sertolli cells function Testosterone (T4) - 100 to 500x higher in the seminiferous tubules Estradiol (E2) – Sertoli cells function Inhibin (INH) – secreted by Sertolli cells Androgen binding proteins (ABP) - secreted by Sertolli cells, ensure a constant high intratubular concentration of testosterone VetPrep MM In summary Vet Prep MM The ability of the hypothalamus to produce GnRH triggers puberty Peptide/protein hormones can cause supraphysiological stimulation/”downregulation” Steroid hormones have delayed action but a longer half-life Female have both centers of the hypothalamus males Estradiol cause a positive feedback to the Surge center of the hypothalamus Surge center of the hypothalamus is essential for ovulation Inhibin is produced by the dominant follicle and induces follicular deviation Oxytocin binds the endometrial receptors and induce luteolysis in non-pregnant females (production of PGF2α) Testosterone controls the release of GnRH by the hypothalamus in males Testosterone is 100-500 x higher in the seminiferous tubules than in the blood Lorenzo Segabinazzi, DVM, MSc, PhD Ross University School of Veterinary Medicine THANK YOU VETERINARY.ROSSU.EDU [email protected] ©2021 Ross University School of Veterinary Medicine. 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