L24: Hormones Affecting Reproduction

What regulates the overall reproduction in animals by synthesis and release of hormones?

hypothalamus

Which hormones are produced by the hypothalamus?

gonadotropin-releasing hormone (GnRH);
dopamine

What is the primary function of gonadotropin-releasing hormone and dopamine?

stimulate or inhibit the release of specific anterior pituitary hormone

How do hypothalamic hormones reach the anterior pituitary?

hypothalamic-adenohypophyseal portal system

What is the function of the pituitary gland?

regulation of production, growth, stress, intermediary metabolism

What types of reproductive hormones does the anterior pituitary gland release?

gonadotropins;
prolactin

What are the gonadotropins released by the anterior pituitary?

follicle-stimulating hormone (FSH);
luteinising hormone (LH)

What is the function of FSH and LH?

stimulate secretion of gonadal steroids

What are the main sources of reproductive steroid hormones?

ovaries (female);
testes (male)

What are the main reproductive steroid hormones in females?

oestrogen; progesterone

What is the main reproductive steroid hormone in males?

testosterone

Which hormones regulate the oestrus cycle?

GnRH, FSH, LH

What effect do oestrogens and progesterone have?

stimulatory effect of endometrium and mammary gland;
decreases gonadotropin release (negative feedback)

What phases are there in the oestrus cycle?

follicular phase (proestrus and oestrus);
luteal phase (metestrus and dioestrus)

What happens during the follicular phase?

ovarian follicles develop and mature secreting increasing amounts of oestrogen, which triggers release of LH from pituitary gland, causing ovulation of follicles and release of ova to the oviduct

What happens in the luteal phase?

remnants of follicle becomes corpus luteum, which secretes progesterone to create an environment compatible with implantation of the embryo;
fertilised corpus luteum results in continued progesterone secretion;
when not fertilised, endometrium releases prostaglandin F2α causing corpus luteum regresses ceasing secretion of progesterone

What can be used to stimulate the gonad in either sex?

GnRH;
human chorionic gonadotropin (HCG);
pregnant mare serum gonadotropin (PMSG);
pituitary gonadotropins (FSH);
prolactin;
oxytocin

What is the release of GnRH controlled by?

neural pulse generator in the hypothalamus

What regulates GnRH production and by what mechanism?

gonadotropins, gonadal steroids;
negative feedback

What is the clinical use of GnRH?

management of infertility;
suppression of gonadotropin secretion (medical castration)

What are the synthetic GnRH?

gonadorelin;
leuprolide

What is gonadorelin?

synthetic GnRH

What is Gonadorelin used for?

infertility therapy;
cystic ovaries therapy;
oestrus synchronisation in conjunction with PGF2α;
timed embryo transfer;
terminating oestrus;
diagnostic purposes;
identifying intact animals

What is leuprolide?

long-acting GnRH analogue

What controls the synthesis and release of gonadotropins?

GnRH

What type of cells synthesise and secrete gonadotropins?

gonadotropes

Which animals are HCG and PMSG secreted in?

primates, horses

Where are HCG and PMSG secreted from?

syncytiotrophoblast cells in placenta

What cause the inhibition of secretion of gonadotropins?

gonadal steroid hormones (androgens, oestrogens, progesterone)

What effect does LH have on males?

acts on testicular Leydig cells to stimulate synthesis of androgens (testosterone)

What effect does FSH have on males?

acts on Sertoli cells to stimulate the production of proteins and nutrients required for sperm maturation

What effect does FSH have on females?

stimulate growth and development of follicles;
induce ovulation and stimulate follicle to produce oestrogen

What effect does LH have on females?

stimulates further development of ovarian follicles;
induce ovulation and stimulate follicle to secrete progesterone (after ovulation)

What are the therapeutic uses for gonadotropins?

female and male fertility;
cryptorchidism (hidden or obscure testes)

What is HCG used for?

infertility therapy;
cystic ovaries;
inducing oestrus cycles;
impotence;
cryptorchidism;
inducing pseudopregnancy

What toxic effects can hCG have?

anaphylaxis due to antihormone antibody;
prolonged usage may cause loss of efficacy

What is PMSR used for?

ovarian follicular growth;
inducing oestrus cycle

What is human menopausal gonadotropin (hMG)?

extracted from urine of postmenopausal women, which has equal amounts of FSH and LH activity

What is FSH used for?

superovulation;
oocyte collection;
production of embryos used in embryo transfer procedures

What is prolactin?

promotes mammary gland development and milk production;
prevents ovulation

Where is prolactin synthesised and secreted from?

lactotropes in anterior pituitary gland

How is the release of prolactin regulated?

release of dopamine from the hypothalamus

Is prolactin used therapeutically?

no

What drugs can affect prolactin and how?

metoclopramide (antiemetic) and domperidone (stimulate gastric motility);
dopamine antagonists

What is oxytocin?

causes increased contraction of the uterus during labour and stimulates the ejection of milk into the ducts of the breasts

Where is oxytocin synthesised?

hypothalamus;
corpus luteum (cow, ewe, primates)

Where is oxytocin stored and secreted from?

posterior pituitary gland

What stimulates the release of oxytocin?

sensory stimuli of cervix and vagina;
suckling of mammary gland

What causes inhibition of oxytocin stimulatory function?

progesterone

What is oxytocin used for?

labour induction;
milk let down;
combat uterine inertia during delivery;
aid in treatment of mastitis or pyometra

What are the toxic effects of oxytocin?

overdose or repeated dosing can lead to painful contractions and uterine rupture causing foetal death

What should be used in small animals instead of oxytocin?

prostaglandins

Where are prostaglandins produced?

in most major tissues

What are prostaglandins synthesised from?

arachidonic acid

What enzyme is involved in the formation of prostaglandins?

phospholipase A2

Where is the primary source of prostaglandin F2α (PGF2α)?

endometrium (large animals)

What does PGF2α do?

mediates decrease in circulating progesterone via luteolysis and decreased placental progesterone production

What roles do prostaglandins have?

ovulation, luteolysis, gamete transport, uterine motility, contractions, expulsion of foetal membranes and sperm movement

Why is PGF2α used?

luteolytic effect;
decrease oestrus cycle length;
induce abortion and parturition

What is the form of prostaglandins used clinically?

dinoprost

What are the clinical uses of dinoprost?

oestrus synchronisation;
abortion and parturition;
uterine contractions;
mating-induced persistent endometritis;
uterine infections;
inducing parturition

What are the adverse reactions of dinoprost?

increased smooth muscle tone: diarrhoea, abdominal discomfort, bronchoconstriction, increased blood pressure;
vomiting;
ataxia;
anxiety;
salivation;
hyperpnea

What is the major ovarian oestrogen?

oestradiol

What are the natural oestrogens?

oestradiol, oestrone, oestriol

How are oestrogens transported in the blood?

sex hormone-binding globulin (SHBG)

What is the semisynthetic derivative of oestradiol?

ethinyl estradiol

What is the synthetic oestrogen?

mestranol

What is the nonsteroidal derivative of oestrogen?

diethyl stillbosterol (DES)

What are the therapeutic uses of oestrogen?

uterine infections and involution;
oestrus synchronisation;
metritis in cattle;
parturition induction in horses;
urinary incontinence and perianal gland adenoma in dogs

What is the major progestin in humans and animals?

progesterone

What are the sources of progesterone?

corpus luteum; placenta (in some animals)

What are the synthetic progestins?

altrenogest;
melengestrol acetate (MGA)

What is altrenogest indicated for?

suppress oestrus in mares;
minimise abortions in low doses;
facilitate artificial insemination;
synchronising oestrus in pig (under 1 year of age)

What are the contraindications of altrenogest?

pregnant mares because higher doses cause foetal abnormalities

What is Syncro-Mate-B?

progesterone-oestrogen combination for oestrus synchronisation

What is melengestrol acetate?

synthetic progestin-based feed-additive system to synchronise oestrus in cattle

What is CIDR?

(controlled internal drug release) intravaginal progesterone-releasing device for cattle, sheep, goats for synchronisation of oestrus

What is PRID?

Progesterone Releasing Intravaginal Device for synchronisation of oestrus and ovulation in cattle

What is the principle circulating androgen in males?

testosterone

Where is testosterone secreted?

Leydig cells of testes

What stimulates the release of testosterone?

LH from pituitary

What is the role of testosterone?

regulates male reproductive system;
sexual differentiation

What are the natural testosterone derivatives?

dihydroxytestosterone;
oestradiol

What are anabolic steroids?

synthetic testosterone analogues with greater anabolic and androgenic effects

What are examples of alkylated anabolic steroids?

stanazolol;
oxymathalone;
norethandrolone

What are examples of nonalkylated anabolic steroids?

nandrolone;
methenolone

What is the major indication for anabolic steroids?

increase athletic performance (horses);
increase muscle size and strength;
increase RBC production;
increase positive nitrogen balance

What can anabolic steroids be used to treat and why?

aplastic anaemia;
myeloproliferative disease;
lymphoma accompanied by non regenerative anaemia;
they increase myelopoiesis, stimulate production of erythropoietic, and increase production of erythrocytes

What groups can anabolic steroids be classified into?

alkylated;
nonalkylated

What are examples of specific reproductive conditions?

superovulation;
pseudopregnancy;
parturition;
abortion;
cryptorchidism

What is superovulation?

Hormonal treatment to increase number of ovulations so embryos can be transferred to increase progeny

How many follicles can be ovulated in superovulation?

10 (results in 6 viable embryos)

How does superovulation occur?

injection program is begun between 9 and 14 days of the oestrus cycle;
FSH is given over 4 days;
PGF2α is given on days 3 and 4

How is pseudopregnancy induced in queens?

GnRH or hCG

How is parturition induced in cattle?

glucocorticoids (dexamethasone or flumethasone) and PGF2α (cloprostenol)

What are the reasons for inducing parturition?

allowing more time postpartum before the next breeding;
attempting to reduce calf size and dystocia;
preventing excessive udder oedema in dairy cattle;
taking advantage of available forage for milk production

How is parturition induced in horses?

oxytocin

What drug can be given during oestrus to prevent pregnancy?

oestrogens (diethyl stillbestrol);
tamoxifen

Is a dog is known to be pregnant, which drugs can be used to terminate pregnancy?

prostaglandins;
inhibitors of prolactin secretion or dexamethasone;
progesterone receptor blockers

What are examples of inhibitors of prolactin secretion used in the termination of pregnancy?

cabergoline, bromocriptine, metergoline