Hormones of Reproductive

Systems

Group Victors

S. No. Topics Presented By-

1. Introduction of Reproductive System Devendra Pandey

2. Menstrual Cycle Maulik Bhai Patel

3. Estrogen Axar Parmar

4. Progesterone Jagdish Prajapati

5. Follicle Stimulating Hormone Sanket Patel

6. L Hormone Reema Sansare

7. H C G Abhinandan Jadhav

8. Prolactin Trupti Mulik

9. Oxytocin Rohan Desai

10. Androgen Mayur Amin

• The ability to reproduce is one of the properties which distinguishes living from non-living matter.

• The reproductive system is a system of organs within an organism which work together for the purpose of reproduction.

• The Major organs include-

a. genitalia (penis and vulva)

b. Internal organs (testicles and ovaries)

• Both males and females produce specialised reproductive germ cells, called gametes. The male gametes are called spermatozoa and the female gametes are called ova.

Female Reproductive Systems Male Reproductive Systems

• Formation of female gametes, ova

• Reception of male gametes, spermatozoa

•Provision of suitable environments for fertilisation of the ovum by spermatozoa and development of the resultant fetus

• Parturition (childbirth)

• Lactation, the production of breast milk, which provides complete nourishment for the baby in its early life.

• production of male gametes, spermatozoa

•transmission of spermatozoa to the female.

• Some Important Parts are-• Scrotum• Testes• Spermatic Cords• Seminal Vesicles• Prostate Glands• Urethra & Penis

• External Genitalia (Vulva)- Labia majora, Labia minora, Clitoris, The vaginal orifice The vestibule, hymen and the vestibular glands.

• Internal Genitalia- Vagina Uterine Tube (Fallopian Tubes)

Uterus Ovaries

• The breast is the upper ventral region of an animal’s torso, particularly that of mammals, including human beings. The breasts of a female primate’s body contain the mammary glands, which secrete milk used to feed infants.

• 1 Anatomy – 1.1 Lymphatic drainage. – 1.2 Shape and support. – 1.3 Development.

• 2 Function – 2.1 Breastfeeding. – 2.2 Sexual role.

FEMALE REPRODUCTIVE CYCLE

- MAULIKBHAI PATEL

FEMALE REPRODUCTIVE CYCLEThe cyclic events that take place in a rhythmic

fashion during the reproductive period of woman’s life is called “Female Reproductive Cycle”.

Duration: 28 days (24 - 35 days)

– Absent upto 12-14 years

– Again stops after 45-50 years

Phases:

– Menstrual Phase (1 – 5 day)

– Pre ovulatory Phase (6 – 13 day)• Ovulation (14 day)

– Post ovulatory Phase(15 – 28 day)

Biochemistry of gonadal hormones (Estrogen)

ByAxar Parmar

Estrogen

• Estrus + gen/gonos• Steroid hormones produced predominantly by the

ovaries.• Although the adrenals, placenta, and other organs

may contribute. • Roles in both males and females.

– Males: growth spurt, skeletal maturation, maturation of sperm, healthy libido.

– Females: development of female sex organs and secondary sex characteristics, regulate menstrual cycle, skeletal maturation.

Types

(1) Steroidal

(2) Non-steroidal

CH3OH

H

H

H

HO

ESTRADIOL

CH3

H

H

H

HO

O

ESTRONE

CH3OH

H

H

H

HO

OH

ESTRIOL

Steroidal Estrogens

Non-steroidal Estrogens

• Xeno-estrogens

• Phyto-estrogens

• Myco-estrogens

Bio-synthesis

• 1⁰-Developing follicles in the ovaries, the corpus luteum, and the placenta.

• Follicle-stimulating hormone (FSH) and luteinizing hormone (LH).

• Other tissues - Liver, adrenal glands, and the breasts.

Estrone(produced in both male and female

adipose cells)

Pathways for the synthesis of testosterone (testes) and the estrogens estradiol (ovaries) and estrone (adipose cells)

Cholesterol Pregnenolone Progesterone

Progesterone Androstenedione Testosterone(pathway ends here in testes)

Estradiol(pathway continues to here

in ovaries)

Aromatase

Aromatase

Target Tissues in Females & Males

Also: Colon (& Intestine) Bladder & Urogenital Tract Lung

Korach, 2001

Actions of estrogens

• On sexual organs (primary and secondary sexual characteristics)

• ovaries : stimulate follicular growth; small doses cause an increase in weight of ovary; large doses cause atrophy

• uterus: endometrial growth• vagina: thickening and stratification of

epithelium• cervix: increase of cervical mucous with a

lowered viscosity (favoring sperm access)

Actions of estrogens• Development and maintenance of internal

(fallopian tubes, uterus, vagina), and external genitalia

• skin: increase in vascularization, development of soft, textured and smooth skin

• bone: increase osteoblastic activity• electrolytes: retention of Na+, Cl- and water by

the kidney• cholesterol: hypocholesterolemic effect (↑HDL,↓ LDL)• GI Tract: reduction of bowel motility

Medical Uses of Estrogen

• Oral contraceptives• Menopausal hormone

therapy (Bone, Vagina, Heart)• Breast Cancer• Prostate Cancer• Hypoestrogenism• Wound healing

Steroidal Estrogenic Drugs:• Estradiol:

– Most active natural estrogen.– Very short duration of action due to first pass metabolism.– Mainly used for local effect on the uterus.

• Ethinyl estradiol:– 15- 20 more potent than estradiol orally.

HO

OHC CH

HO

OH

17-estradiol Ethinyl estradiol(Stertoidal Semisynthetic estrogen)

Nonsteroidal Estrogens• Diethylstilbesterol:

– The trans form is the active one.– Advantages:

• As active as Estradiol.• Longer duration of action.• Orally active• Cheap.

– Disadvantages:• Increase the risk of uterine cancer.

– Uses:• Treatment of prostate cancer.

OH

HO

PROGESTERONE

BY : - JAGDISH PRAJAPATI

Progesterone(pregn-4-ene-3,20-dione)

• Steroid hormone synthesized predominantly by the

corpus luteum and placenta during the

postovulatory or luteal phase of the menstrual cycle.

• During pregnancy, the placenta takes over the

production of progesterone.

• The adrenal cortex is also a source of small amounts

of progesterone.

SYNTHESIS OF PROGESTERONE

EFFECTS OG PROGESTERONE

• Reproductive system• Nervous system• Thermogenic function• Smooth muscle

• As OCS

• HRT

• Dysmenorrhoea

• Premenstrual syndrome

• Endometriosis

• Threatened abortion

• post-partum lactation

• Endometrial cancer

Clinical uses of Progesterone

Adverse effects of Progesterone• Breast enlargement, headache, rise in body temp.,

oedema, acne & mood swings

• Masculinization of external genitalia in the foetus

• Increased incidences of congenital abnormalities

• Irregular bleeding or amenorrhea

• Lower HDL (19-nortestosterone derivatives)

• Hyperglycemia

METABOLISM OF PROGESTERONE• Progesterone undergoes high first pass metabolism.

Therefore synthetic preparations are more commonly used.

• Progesterone esters in oily solution for i.m. administration

• Plasma half life :- 5 minute

DRUGS

PROGESTERONE AGONISTS

• Prometrium

• Prochieve

• Crinone

PROGESTERONE ANTAGONISTS

• Mifepristol

Mifepristone• 19-nor-steroid derivative

Mechanism:

• Blocks progest. &

glucocorticoid receptors

• During luteal phase:

Pregest. PGs

Menstrual bleeding

• Sensitize myocardium to PGs.

• HCG production falls

Uses:

• Termination of early pregnancy – along with prostaglandin

• Post-coital contraceptive

• Once a month contraceptive

• Progesterone sensitive tumors

• Cushing’s syndrome

Side effects:

Vomiting, diarrhoea, pelvic pain or abdominal pain, about 5% have severe vaginal bleeding

Precaution: Not to be given to a woman with suspected ectopic pregnancy, hematological disorders, receiving oral anticoagulants,Liver/renal diseases

Follicle Stimulating Hormone

By Sanket Patel

Introduction

• It is synthesized and secreted by gonadotropes of the Anterior Pituitary Gland.

• FSH regulates the development, growth, pubertal maturation, and reproductive processes of the body.

• FSH and Luteinizing Hormone (LH) act synergistically in reproduction.

Biochemical Structure• FSH is a glycoprotein.• The Protein Dimer contains 2 polypeptide units,

labeled alpha and beta subunits. • The alpha subunits contain 92 amino acids.• The beta subunits vary but generally contain 118

amino acids.• The sugar part of the hormone is composed of

fructose, galactose, mannose, galactosamine, glucosamine and sialic acid.

• The Half-life of FSH is 3-4 hours. Its molecular wt is 30,000.

Biochemical Functions

• In both males and females, FSH stimulates the maturation of germ cells.

• In males, FSH stimulates maturation of seminiferous tubules and spermatogenesis.

• In males, FSH enhances the production of androgen-binding protein by the Sertoli cells of the testes and is critical for spermatogenesis.

• In females, FSH initiates follicular growth, increases the weight of the ovaries and enhances the production of estrogens.

High FSH Levels

• Premature menopause also known as Premature Ovarian Failure

• Poor ovarian reserve also known as Premature Ovarian Aging

• Gonadal Dysgenesis or Turner syndrome • Castration • Certain forms of CAH • Testicular failure.

Low FSH Levels

• Polycystic Ovarian Syndrome • Polycystic Ovarian Syndrome + Obesity +

Hirsutism + Infertility • Kallmann syndrome • Hypothalamic suppression • Hypopituitarism• Hyperprolactinemia • Gonadotropin Deficiency

•Luteinizing Hormone

Definition

• Luteinizing hormone (LH), also known as lutropin is a hormone produced by the anterior pituitary gland.

• In the female, an acute rise LH – the LH surge – triggers ovulation.

• In the male, where LH had also been called Interstitial Cell Stimulating Hormone (ICSH),it stimulates Leydig cell production of testosterone.

Functions

• In Female,– it controls the length and sequence of the female

menstrual cycle, – including ovulation, – preparation the uterus for implantation of a

fertilized egg, and – ovarian production of both estrogen and

progesterone. • In males,

– it stimulates the testes to produce androgen.

STRUCTURE

• LH is a heterodimeric glycoprotein.

• Each monomeric unit is a glycoprotein molecule;– one alpha and

– one beta subunit make the full, functional protein.

• The protein dimer contains 2 glycopeptidic subunits, labeled alpha and beta subunits, that are non-covalently associated (i.e. without any disulfide bridge linking them).

STRUCTURE Cont…

• The alpha subunits of LH contain 92 amino acids in human but 96 amino acids in almost all other vertebrate species (glycoprotein hormones do not exist in invertebrates).

• The beta subunits vary. LH has a beta subunit of 121 amino acids (LHB) that confers its specific biologic action and is responsible for the specificity of the interaction with the LH receptor.

SYNTHESIS

AVAILABILITY• LH is available mixed with FSH in the form of

Pergonal, and other forms of urinary gonadotropins .

• Recombinant LH is available as lutropin alfa (Luveris).

• All these medications have to be given parenterally.

• They are commonly used in infertility therapy to stimulate follicular development, notably in IVF therapy.

Diseases related with the efficiency of LH

• Diminished secretion of LH can result in failure of gonadal function (hypogonadism).

• This condition is typically manifest in males as failure in production of normal numbers of sperm.

• In females, amenorrhea is commonly observed.

Human Chorionic Gonadotropin

Human Chorionic Gonadotropin

• A hormone produced by the placenta that during the pregnancy

• HCG is shows up in urine and in blood (HCG is what shows up in pregnancy tests)

• HCG is measured in term of mlu/ml.

Structure of HCG

Weeks after LMP HCG levels for single baby

( in mIU/ml )

3 weeks 0 to 5

4 weeks 5 to 426

5 weeks 18 to 7340

6 weeks 1080 to 56500

7-8 weeks 7650 to 229000

9-12 weeks 25700 to 288000

13 to 16 weeks 13300 to 254000

17 to 24 weeks 4060 to 165400

25 weeks to childbirth

3640 to 117000

How HCG level increases

HCG level in mIU/ml Requited time to double

Below 1200 48-72 hrs

Between 1200-6000 72-96

Above 6000 96<

How HCG help in pregnancy report

HCG level in mlu/ml Report

5 Negative

5-25 Positive / Negative

25< Positive

Functions

1. To support the corpus luteum producing progesterone when conception occurs.

2. Accelerate ovulation & formulation of corpus luteum & to increase animal sexual desire.

3. Stimulation of ovulation in females.4. In hypogonadism ( lack of function of the

gonad ovaries).

Side effects

1 Gynecomastia (the development of abnormally large mammary gland in males)

2 Head ache3 Depression4 Restlessness & tiredness5 Oedema

PROLACTIN

PROLACTIN

Prolactin (PRL) or Luteotropic hormone (LTH) is a peptide hormone discovered by Dr. Henry Friesen.

Prolactin is secreted by the anterior pitutary gland.

Prolactin stimulates in milk production and secretion.

PROLACTIN (PRL)

PRESCRIPTION DRUGS FOR INCREASING MILK SUPPLY

Metoclopramide

Domperidone

Sulpiride

ANOVULATION

DEFINITIONAnovulation is a condition in which the ovary does not release a ripened egg each month as part of a woman's normal cycle in her reproductive years. Naturally, with no egg available for sperm, a woman cannot become pregnant. Thus, anovulation is a prime factor in infertility.

CAUSES AND RISK FACTORS

Hyperprolactinemia.

Excessive exercise and weight loss. Suppresses the output of hormones called gonadotropins from the hypothalamus in the brain.

Oral contraceptive pills. Disrupts the hypothalamic-pituitary-ovarian axis, suppressing ovulation and thereby preventing pregnancy.

DRUGS

Bromocriptine- suppresses prolactin level

Clomiphene citrate (Clomid) - induces ovulation, by relaese of

FSH (follicle stimulating hormone)

OXYTOCIN

Oxytocin (sold as Pitocin, Syntocinon) is a mammalian hormone that also acts as a neurotransmitter in the brain.

OXYTOCIN:Produced predominantly by the Para Ventricular Nucleus (PVN) of the Hypothalamus.

STRUCTURE

Chemical Data

FORMULAC43H66N12O12S2

MOLECULAR MASS1007.19g/mol

HALF-LIFE3 minutes in blood

SynthesisOxytocin is made in magnocellular neurosecretory cells of the supraoptic and paraventricular nuclei of the hypothalamusIn the pituitary gland, oxytocin is packaged in large, dense-core vesicles, where it is bound to neurophysin IOxytocin is also made by some neurons in the paraventricular nucleus that project to other parts of the brain and to the spinal cord

Oxytocin structure. Inset shows oxytocin bound to neurophysin

Drugs form & drugs containing oxytocin

Trade names Pitocin and SyntocinonDosage form: injectables & nasal sprayInjected oxytocin analogues are used to induce labor and support labor in case of non-progression of parturition.

It is best known for its roles in female reproduction:

released in large amounts after distension of the cervix and vagina during labor, and after stimulation of the nipples, facilitating birth and breastfeeding.

Oxytocin is also used in veterinary medicine to facilitate birth and to increase milk production.

OXYTOCIN : FUNCTIONS

OXYTOCIN : FUNCTIONS contd

ON THE BREAST :Causes Milk ejection and secretion through a Neuro-endocrine reflex.

OXYTOCIN: FUNCTIONS contd

ON THE NON PREGNANT UTERUS:– Movement of the Female Genital Tract– Transport of the Sperm– Fertilization

ON THE PREGNANT UTERUS:Initiates Parturition or Labour.Enhances Uterine contractions during labor.Stretches the birth canal by a Positive feedback mechanismCauses involution of the Uterus after delivery.

OXYTOCIN:FUNCTIONS contd

ANDROGENS (Male Sex Hormones)

Mayur Amin

TYPES OF ANDROGENS

• Testosterone

• Dehydroepiandrosterone

• Dehydroisoandrosterone

• Androstenedione

BIOSYNTHESIS

Cholesterol

Dehydroepiandrosterone

Pregnenolone

17-α-Hydroxy Progesterone

Androstenedione

Progesterone

Dehydrogenase/Isomerase

Testosterone

17-α-Hydroxy Progesterone

PHYSIOLOGICAL FUNCTIONS

Sex related physiological functions

Growth, Development & Maintenance

Sexual Differentiation

Spermatogenesis

Aggressive Behavior

BIOCHEMICAL FUNCTIONS

Effects on protein metabolism

Effects on carbohydrate and fat

metabolism

Effects on mineral metabolism

TESTOSTERONE DEFICIENCY

Hypogonadism

Klinefelter’s syndrome

Kallmann’s syndrome

Gynaecomastia

Gynaecomastia

• Enlargement of the breast tissue beneath the areola • Common among elderly men• Associated weight gain. • Half of males experience enlargement of one or both

breasts• Can be the first sign of testicular tumor

Medical evaluation is always indicated whenBreast enlargement occurs

• More common in patients with klinefelter's syndrome• Pseudogynaecomastia

breast enlargement due to fat accumulation.

Bibliography• The Pharmacological Basis of Therapeutics by Goodman and Gilman

• “Perspective: Female Steroid Hormone Action” by Dr. Orla Conneely• <http://wikipedia.com>• “Progesterone vs Progestin” by Dr. Steven Hotze• <http://www.cancer.gov>• “Advances in HRT: Weight benefits of drospirenone, a 17α –spirolactone-derived

progestogen” by Foidart, et al. • “Estrogens and the skin” by Brincat, et al.

• <http://www.providence.org>