Endocrinology of Reproduction I and II

Reading

• Chapter 5
• Handout 4
• Any addition lecture diagrams or pictures not in text

Endocrine System:

• function
• neurohumoral interaction

Manipulation of the Endocrine System

• growth stimulators (DES
• lactation stimulators (GH or STH)
• birth control (DES, Estradiol, Progesterone)
• estrous cycle regulation (PGF)
• superovulation and embryo transplant (FSH, PMSG)
• induction of parturition (oxytocin, dexamethazone)

Definitions:

• endocrine glands
• exocrine glands
• hormone
• endocrinology

Endocrine Glands

• name, location, hormone produced, function

Classification of hormones

• Type of action
  1. Primary hormone of reproduction (FSH, LH, estradiol, progesterone)
  2. Metabolic hormone (thyroxin, insulin, STH)
• Chemical Structure
  1. Proteins and polypeptides (hypothalamic and pituitary hormones)
  2. Steroids (gonadal and adrenal)
  3. Fatty acids (prostaglandins)
  4. Modified amino acid (melatonin)

Hypothalamus - Releasing Hormones of the Hypothalamus

• Structure
  1. short chain polypeptides (3 - 44 amino acids)
• General Function
  1. to cause the release of trophic hormones from the anterior pituitary gland
• Hormones
  1. Gonadotrophin releasing hormone (GnRH) - releases of FSH and LH from anterior pituitary
  2. Thyrotrophin releasing hormone (TRH) - releases TSH and prolactin from anterior pituitary
  3. Corticotrophin releasing hormone (CRH) - releases ACTH from anterior pituitary
  4. Growth hormone releasing hormone (GH-RH) - releases growth hormone from anterior pituitary
  5. Somatostatin (growth hormone inhibiting hormone) - inhibits growth hormone release from anterior pituitary

Hypothalamic Hormones Released in the Posterior Pituitary

• Structure
  1. polypeptides (9 amino acids)
• Hormone
  1. Oxytocin - causes contraction of smooth muscle such as in mammary gland, uterus, oviduct
• Other facts of importance
  1. produced in the hypothalamus but secreted in posterior pituitary
  2. also produced in the corpus luteum of some species

Anterior Pituitary Hormones

• Structure
  1. glycoproteins or proteins
• Hormones
  1. Gonadotrophins
     • Follicle stimulating hormone (FSH) - stimulates follicle growth and spermatogenesis
     • Luteinizing hormone (LH) - causes ovulation and maturation of oocyte, maintains the corpus luteum, stimulates androgen secretion by leydig cells
     • Prolactin - in rodents helps to maintain CL, stimulates maternal behavior
  2. Other trophic hormones
     • Corticotrophin (ACTH) - stimulates cortisol release from adrenal gland
     • thyroid stimulating hormone (TSH) - stimulates thyroxine release from thyroid gland
     • growth hormone (GH or STH) - growth of long bones, lactation

Placental Hormones

• equine Chorionic Gonadotropin (eCG, once called PMSG)
  1. Contains mainly FSH-like activity but also some LH-like activity.
  2. Has a longer half-life than FSH.
  3. Found in the blood and not the urine.
  4. Function
     • stimulates follicular development during pregnancy in the mare
     • the LH-like activity stimulates some developing follicles to ovulate and form accessory CLs
  5. Other commercial hormones from the equine placenta
     • estrogens
       • found in mare urine
       • Premarin is the commercial product
       • treatment of postmenopausal women
         • estrogen replacement therapy
         • prevention of osteoporosis
         • prevention of heart disease
• Human Chorionic Gonadotropin (HCG)
  1. Has LH-like activity.
  2. Found in blood and urine.
  3. Function
     • prevents CL regression
• Placental Lactogen (PL)
  1. Has both GH- and prolactin-like activity. The primary effect is to prepare the mother's mammary gland for lactation.

Gonadal Polypeptide Hormones

• Relaxin
  1. Made of 2 polypeptides that are connected with disulfide bonds. It is similar in size and structure to insulin.
  2. Secreted by CL during pregnancy.
  3. In some species it may be secreted by the uterus and/or placenta.
  4. Generally requires tissue first be exposed to estrogens for its effects.
  5. Functions
     • cervical dilation
     • inhibits uterine contractions
• Inhibin
  1. Secreted by sertoli cells in the male and granulosa cells in the female.
  2. Function
     • inhibits FSH secretion without altering LH secretion

Gonadal Steroids

• General
  1. Origin - ovary, testis, adrenal
  2. Basic structure
  3. Type of activity can be predicted by structure
     • estrogen - 18 carbons
     • progestin - 21 carbons
     • androgen - 19 carbons
     • cholesterol - 27 carbons
• Steroid Synthesis
• Androgens
  1. An example is testosterone.
  2. Produced by Leydig cells in the testis, theca interna in the follicle and by the adrenal gland.
  3. Transported in the blood by binding to the protein, steroid binding globulin.
  4. Active form is often dihydrotestosterone.
  5. Function in the male
     • stimulates spermatogenesis
     • maintain the function of the epididymis
     • promotes the growth, development, and activity of accessory sex glands and secondary sex organs
     • development of male secondary sex characteristics
     • anabolic activity
     • inhibits GnRH release
• Estrogens
  1. An example is estradiol.
  2. Produced by granulosa cells of the follicle, sertoli cells in the testis, the placenta, and the adrenal gland.
  3. Transported in blood by steroid binding globulin
  4. Functions
     • effects on the CNS
     • increases the mass of the uterus
     • increases the contractility of the uterus
     • development of female secondary sex characteristics
     • growth of the mammary gland ducts
     • stimulates or inhibits GnRH release
     • nonreproductive
       1. calcium uptake and bone ossification
       2. anabolic and growth effects
• Progestins
  1. An example is progesterone
  2. Produced in the CL, the placenta and the adrenal gland.
  3. Transported in the blood bound to steroid binding globulin.
  4. Functions
     • prepares the uterus for implantation and pregnancy
     • acts with estrogen to induce the behavior patterns of estrus
     • develops alveoli of mammary gland
     • inhibits the rise of LH that causes ovulation

Prostaglandins

• An example is PGF
• Produced in many tissues and organs but generally acts locally although it can have effects through the vascular system.
• Function
  1. to regress the CL
  2. contraction of the uterus

Melatonin

• Secreted from the pineal gland.
• Is a modified amino acid
• Functions to integrate effects of light on reproductive processes.

Human Memopausal Gonadotropin (hMG)

• Secreted from the anterior pituitary gland during and after menopause.
• Has FSH-like activity and is actually a modified FSH molecule with a longer half-life. Results from lack of estradiol feedback.
• Can be collected in the urine and sold to stimulate follicular development in women.

Classification of Hormones by Chemical Structure

polypeptide	modified amino acid	protein	sex steroid	fatty acid
GnRh	melatonin	Relaxin	Estradiol	PGF
TRH		Inhibin	Progesterone
CRH		Prolactin	Testosterone
GHRH		ACTH
Somatistatin		TSH
Oxytocin		GH or STH
		FSH
		LH

Molecular Size of Hormones that Regulate Reproduction

Hormone	Molecular Weight
FSH	30,000 to 37,000
LH	26,000 to 32,000
Prolactin	23,000 to 25,000
ACTH	4,500
Inhibin	>10,000
Oxytocin	1,007
GnRH	1,200
HCG	37,700
PMSG	28,000
Relaxin	6,500
Estradiol	300
Testosterone	300
Progesterone	300
PGF	300

Polypeptide and protein hormones (Figure 1)

• made of peptide bonds
• these hormones can be not be fed orally.

Steroid Hormones (Figure 2)

• made in ovary, testis and adrenal
• adrenal can convert progesterone from ovary into steroids
• can have problems if adrenal produces large quantities of sex steroids

Mechanism of Hormone Action

• requires that hormone bind to target cell
• target cells have the receptor for the hormone
• protein hormones - plasma membrane receptors
  • cAMP second messenger hormones (Figure 3)
    • FSH, LH, Prolactin
  • calcium second messenger hormones (Figure 4)
    • GnRH, Oxytocin, PGF
• steroid hormones - nuclear receptors (Figure 5a)
• steroid hormones - plasma membrane receptors (Figure_5b)
• feedback loops (Figure 6)

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