ENZYMES CHEMICAL COMMUNICATIONS Neurotransmitter and Hormones PENDAHULUAN MAKANAN

ENZYMES, CHEMICAL COMMUNICATIONS (Neurotransmitter and Hormones)

PENDAHULUAN MAKANAN DICERNA dalam saluran pencernaan DIMETABOLISME dalam sel • METABOLISME : –KATABOLISME MOLEKUL YG LEBIH BESAR MOLEKUL YG LEBIH KECIL GLUKOSA CO 2 + H 2 O + ENERGI –ANABOLISME = SINTESIS MOLEKUL YG LEBIH KECIL MOLEKUL YG LEBIH BESAR GLUKOSA GLIKOGEN

Discovery of Enzymes Berzelius Sumner Northrup Stanley • 1825 Jon Jakob Berzelius discovered the catalytic effect of enzymes. • 1926 James Sumner isolated the first enzyme in pure form. • 1947 Northrup and Stanley together with Sumner were awarded the Nobel prize for the isolation of the enzyme pepsin.

Letak enzim dalam sel • Berkaitan dengan FUNGSI ORGANEL SEL yang bersangkutan • ENZIM MITOKONDRIAL : Reaksi pengadaan energi, reaksi oksidasi yang menghasilkan energi • ENZIM RIBOSOMAL : Reaksi biosintesis protein • ENZIM INTI : Berkaitan dengan perangkat genetika • ENZIM LISOSIM : Berkaitan dengan proses digestif intrasellular, Destruksi hidrolitik bahan yang tak diperlukan sel • ENZIM MIKROSOMAL : Reaksi hidroksilasi dalam sintesis hormon steroid, Metabolisme dan inaktivasi obat

Enzymes • Enzymes are biological catalysts, or chemicals that speed up the rate of reaction between substances without themselves being consumed in the reaction. • Which are large protein molecules that increase the rates of chemical reactions without themselves undergoing any change. • Enzim adalah biomolekul berupa protein yang berfungsi sebagai katalis (senyawa yang mempercepat proses reaksi tanpa habis bereaksi)

• Enzim merupakan suatu substansi protein yang ada dalam sel dengan jumlah yang kecil dan mampu mempercepat reaksi kimiawi dimana enzim itu sendiri tidak ikut serta dalam reaksi tersebut dan tidak ikut berubah. • Enzim adalah suatu protein dan dihasilkan oleh sel hidup, Enzim adalah protein yang mempunyai fungsi khusus. Enzim bekerja dalam mengkatalisis reaksi kimia(biokimia) yang berlangsung di dalam sel itu sendiri. • Menurut Mayrback (1952) dari jerman, enzim adalah senyawa protein yang dapat mengatalisi reaksi-reaksi kimia dalam sel dan jaringan makhluk hidup. Enzim merupakan biokatalisator artinya senyawa organik yang mempercepat reaksi kimia.

• Enzim merupakan senyawa organik bermolekul besar yang berfungsi untuk mempercepat jalannya reaksi metabolisme di dalam tubuh tanpa mempengaruhi keseimbangan reaksi • Enzim tidak ikut bereaksi, struktur enzim tidak berubah baik sebelum dan sesudah reaksi tetap • Enzim sebagai biokatalisator • Bagian enzim yang aktif adalah sisi aktif dari enzim

Sifat Enzim a. Merupakan protein b. Merupakan biokatalisator. c. Mempercepat reaksi kimia dengan jalan menurunkan energy aktivasi yaitu energy awal yang diperlukan untuk memulai reaksi kimia. d. Enzim bekerja spesifik artinya untuk mengubah atau mereaksikan suatu zat tertentu memerlukan zat tertentu pula. e. Bekerja sangat cepat f. Tidak ikut bereaksi (tidak mengalami perubahan). g. Tidak mengubah keseimbangan reaksi h. Memliki sifat aktif atau sisi katalitik yaitu bagian enzim tempat substrat berkombinasi. i. Substrat asing yang berfungsi menghambat reaksi disebut inhibitor dan yang berfungsi mempercepat reaksi disebut activator.

Berdasarkan tempatnya enzim dikelompokkan menjadi 2 macam, yaitu: 1. Endoenzim, yaitu enzim yang terdapat di dalam sel untuk membantu dalam proses pencernaan dan perombakan zat makanan di dalam sel. 2. Eksoenzim, yaitu enzim yang dikeluarkan oleh sel untuk mengambil zat makanan yang ada di sekeliling sel.

Nama enzim sering kali diturunkan dari nama substrat ataupun reaksi kimia yang di kataliskan dengan akhiran -ase. International Union of Biochemistry and Molecular Biology telah mengembangkan suatu tatanama untuk enzim • Oksidoreduktase: mengatalisis reaksi oksidasi/reduksi • Transferase: mentransfer gugus fungsi • Hidrolase: mengatalisis hidrolisis berbagai ikatan • Liase: memutuskan berbagai ikatan kimia selain melalui hidrolisis dan oksidasi • Isomerase: mengatalisis isomerisasi sebuah molekul tunggal • Ligase: menggabungkan dua molekul dengan ikatan kovalen

Classification and nomenclature Enzymes are usually classified and named according to the reaction they catalyze. The principal classes are as follows. • Oxidoreductases catalyze reactions involving electron transfer, and play an important role in cellular respiration and energy production. Some of them participate in the process of oxidative phosphorylation, whereby the energy released by the oxidation of carbohydrates and fats is utilized for the synthesis of adenosine triphosphate (ATP) and thus made directly available for energyrequiring reactions.

• Transferases catalyze the transfer of a particular chemical group from one substance to another. Thus, transaminases transfer amino groups, transmethylases transfer methyl groups, and so on. An important subclass of this group are the kinases, which catalyze the phosphorylation of their substrates by transferring a phosphate group, usually from ATP, thereby activating an otherwise metabolically inert compound for further transformations.

• Hydrolases catalyze the hydrolysis of proteins (proteinases and peptidases), nucleic acids (nucleases), starch (amylases), fats (lipases), phosphate esters (phosphatases), and other substances. Many hydrolases are secreted by the stomach, pancreas, and intestine and are responsible for the digestion of foods. Others participate in more specialized cellular functions. For example, cholinesterase, which catalyzes the hydrolysis of acetylcholine, plays an important role in the transmission of nervous impulses. See also Acetylcholine.

• Lyases catalyze the nonhydrolytic cleavage of their substrate with the formation of a double bond. Examples are decarboxylases, which remove carboxyl groups as carbon dioxide, and dehydrases, which remove a molecule of water. The reverse reactions are catalyzed by the same enzymes. • Isomerases catalyze the interconversion of isomeric compounds. • Ligases, or synthetases, catalyze endergonic syntheses coupled with the exergonic hydrolysis of ATP. They allow the chemical energy stored in ATP to be utilized for driving reactions uphill.

Kelas Oksidoreduktase (nitrat reduktase) Transferase (Kinase) Tipe reaksi memisahkan dan menambahkan elektron atau hidrogen memindahkan gugus senyawa kimia Hidrolase (protease, lipase, amilase) memutuskan ikatan kimia dengan penambahan air Liase (fumarase) membentuk ikatan rangkap dengan melepaskan satu gugus kimia Isomerase (epimerase) mengkatalisir perubahan isomer Ligase/sintetase (tiokinase) menggabungkan dua molekul yang disertai dengan hidrolisis ATP Polimerase (tiokinase) menggabungkan monomer-monomer sehingga terbentuk polimer

Proses terbentuknya kompleks enzim substrat sebagai berikut: • Mula-mula substrat melakukan kontak dengan enzim yang aktif. • Bila bentuk subtract sesuai dengan bentuk yang aktif dari enzim maka enzim dan substrat melakukan penyatuan. • Penyatuan substrat dengan enzim membentuk kompleks enzim substrat

• Dalam reaksi enzim terjadi lebih dahulu kompleks enzim substrat yang kemudian menghasilkan hasil reaksi dan enzim kembali reaksi hipotesisnya adalah: • Enzim (E) + Substrat (S) = kompleks enzim substrat (ES) = Enzim + hasil reaksi (P)

Terms in Enzyme Chemistry • Cofactor , the non protein part of an enzyme necessary for its catalytic function. • Apoenzyme, the protein (polypeptide) portion of the enzyme. • Coenzyme, a non protein organic molecule, frequently a B vitamin, that acts as a cofactor. • Substrate, the compound on which the enzyme works, and whose reaction it speed up. • Active side, a three-dimensional cavity of the enzyme with specific chemical properties that enable it to accommodate the substrate. • Activation, is any process that initiates or increase the action of an enzyme. • Inhibition, is the opposite-any process that makes an active enzyme less active or inactive.

Enzim • Perbandingan model “induced fit” dan “kunci dan anak kunci” pada pengikatan substrat oleh enzim

product Substrate Kompleks enzim substart Enzim

Kerja dari Enzim enzyme-product complex enzyme-substrate complex substrate enzim product enzim Persamaan atau hipotesis Michaelis-Menten

Enzymes and Reaction Rates Factors that influence reaction rates of Enzyme catalyzed reactions include 1. Enzyme and substrate concentrations 2. Temperature 3. p. H 23

Konsentrasi Enzim

Reaction Rate enzyme concentration 25

Enzymes and Reaction Rates • At low concentrations, an increase in substrate concentration increases the rate because there are many active sites available to be occupied • At high substrate concentrations the reaction rate levels off because most of the active sites are occupied 26

Substrate concentration • The maximum velocity of a reaction is reached when the active sites are almost continuously filled. • Increased substrate concentration after this point will not increase the rate. • Vmax is the maximum reaction rate 27

Substrate concentration • Vmax is the maximum reaction rate • The Michaelis-Menton constant , Km is the substrate concentration when the rate is ½ Vmax • Km for a particular enzyme with a particular substrate is always the same 28

Factors Affecting Enzyme Action: Substrate Concentration • Increasing substrate concentration increases the rate of reaction (enzyme concentration is constant) • Maximum activity reached when all of enzyme combines with substrate 29

Factors Affecting Enzyme Action Maximum activity Reaction Rate substrate concentration 30

Effect of Temperature • Higher temperature increases the number of effective collisions and therefore increases the rate of a reaction. • Above a certain temperature, the rate begins to decline because the enzyme protein begins to denature 31

Suhu • Penelitian ilmiah menemukan kenaikan reaksi enzim menjadi dua kali lipat tiap kenaikan suhu 10ºC dalam batas suhu wajar. Kenaikan suhu tersebut menstimulasi peningkatan energi kinetik pada molekul substrat dan enzim sehingga energi substrat mengalami penurunan saat bertubrukan dengan enzim. Penurunan energi substrat memudahkan molekul terikat pada enzim. Pada suhu yang meningkat ekstrem, enzim bergetar sehingga menyebabkan terputusnya hidrogen dan enzim mengalami denaturasi, yaitu rusaknya bentuk tiga dimensi enzim dan menyebabkan substrat melepaskannya. Akibatnya, aktivitas enzim pun menurun. • Pada manusia, suhu optimum enzim berkisar pada 37ºC, sedangkan tumbuhan mempunyai suhu optimum yang lebih rendah, yaitu 25ºC.

Factors Affecting Enzyme Action Optimum temperature Reaction Rate Low High Temperature 33

Effect of p. H • Each enzyme has an optimal p. H at which it is most efficient • A change in p. H can alter the ionization of the R groups of the amino acids. • When the charges on the amino acids change, hydrogen bonding within the protein molecule change and the molecule changes shape. • The new shape may not be effective. Pepsin is most efficient at p. H 2. 5 -3 while Trypsin is efficient at a much higher p. H 34

Factors Affecting Enzyme Action: p. H • Maximum activity at optimum p. H • Narrow range of activity • Most lose activity in low or high p. H 35

Factors Affecting Enzyme Action Reaction Rate Optimum p. H 3 5 7 9 11 p. H 36

Keasaman • Kadar asam basa sangat mempengaruhi kerja enzim sebab sebagian besar enzim sangat peka terhadap perubahan p. H. Pada kisaran p. H 7, 0, enzim intrasel bekerja sangat efektif. Jika p. H dinaikkan atau diturunkan, aktivitas enzim akan berkurang dengan cepat. Hanya beberapa enzim yang justru bekerja optimal dalam kandungan p. H sangat asam, yaitu pepsin dan amilase.

Inhibitors • • Enzyme inhibitors are substances which alter the catalytic action of the enzyme and consequently slow down or stop catalysis. There are three common types of enzyme inhibition 1. Competitive inhibitors 2. Non-competitive inhibitors 3. Substrate inhibition. 38

Competitive Inhibitors • Competitive inhibition occurs when the substrate and a substance resembling the substrate are both added to the enzyme. • The inhibitor blocks the active site on the enzyme stopping its catalytic action 39

Non-competitive Inhibitors • Non-competitive inhibitors deactivate the active site of the enzyme. • They alter the enzyme so that it can no longer bind to the substrate 40

Effect of inhibitors on the Reaction Rate • For non-competitive inhibitors Vmax is lower but Km is the same. • For competitive inhibitors, Vmax is the same but Km is increased. 41

Substrate Inhibitors • Substrate inhibition occurs when excessive amounts of substrate are present. • Additional substrate sometimes interferes with the ability of substrate molecules to find active sites on enzymes • In these cases the reaction velocity decreases after the maximum velocity has been reached. 42

Inhibitor • Inhibitor adalah zat yang menghambat kerja enzim. Zat tersebut bersifat menghalangi kerja enzim untuk sementara waktu atau secara tetap. Ada dua jenis inhibitor. • Inhibitor kompetitif, seperti sianida. Inhibitor jenis ini bersaing dengan substrat untuk mencapai sisi aktif enzim. Sianida bersaing dengan oksigen untuk mencapai haemoglobin. Sifat hambatannya sementara dan bisa ditanggulangi dengan menaikkan konsentrasi substrat. • Inhibitor nonkompetitif yang menghalangi fungsi enzim dengan cara melekatkan diri pada bagian luar sisi aktif enzim. Dalam kasus semacam ini, enzim tidak bereaksi terhadap substrat. Hambatannya bersifat tetap, tidak terpengaruh konsentrasi substrat.

Keterlibatan dalam penyakit • Oleh karena kontrol aktivitas enzim yang ketat diperlukan untuk menjaga homeostasis, malafungsi (mutasi, kelebihan produksi, kekurangan produksi) enzim tunggal yang penting dapat menyebabkan penyakit genetik. Pentingnya enzim ditunjukkan oleh fakta bahwa penyakit-penyakit mematikan dapat disebabkan oleh hanya malfungsi satu enzim dari ribuan enzim yang ada dalam tubuh kita.

Enzyme Assays Useful in Medical Diagnosis ENZYME NORMAL ACTIVITY BODY FLUID DISEASE DIAGNOSES Alanine amino taransferase (ALT) 3 -17 U/L Serum Hepatitis Acid Phosphatase 2. 5 -12 U/L Serum Prostate Cancer Alkaline Phosphatase (ALP) 13 -38 U/L Serum Liver or Bone disease Amylase 19 -80 U/L Serum Pancreatic disease or mumps 7 -19 U/L Serum 7 -49 U/L Heart Attack or Cerebrospinal Hepatitis Fluid Aspartate Amino Transferase (AST) Lactate Dehydrogenase (LDH) 100 -350 WU/m. L Creatine Phospokinase (CPK) 7 -60 U/L Phospohexose isomerase (PHI) 15 -75 U/L Serum Heart Atack U/L = International Units per Liter, WU/m. L = Wrobleski Units per Milliliter

CHEMICAL COMMUNICATIONS: Neurotransmitter and Hormones • Neurotransmiter adalah senyawa organik endogen membawa sinyal di antara neuron. • Neurotransmitter, a chemical messenger between a neuron and another target cell: neuron, muscle cell, or cell of a gland. • Neurotransmitter merupakan zat kimia yang digunakan untuk merelay, memodulasi, dan menguatkan signal antara neuron dan sel lainnya. • Neurotransmitters merupakan bahan kimia yang diperhitungkan dalam pengiriman sinyal dari satu neuron ke neuron berikutnya di synapses. • Synapse, an aqueous small space between the tip of a neuron and its target cell

• Neurotransmiter merupakan zat kimia yang disintesis dalam neuron dan disimpan dalam gelembung sinaptik pada ujung akson. • Informasi yang dijalarkan di dalam system saraf pusat terutama dalam bentuk potensial aksi saraf disebut impuls saraf, yang melewati serangkaian neuron-neuron, dari satu neuron ke neuron berikutnya. • Sinyal-sinyal saraf dijalarkan dari satu neuron ke neuron berikutnya melalui batas antar neuron (interneuronal junctions) yang disebut sinaps

Three principal types of molecules for communications: • Receptors, are protein molecules on the surface of cells embedded in the membrane. • Chemical messengers, also called ligands, interact with the receptors. • Secondary messengers, in many case carry the message from the receptor to the inside of the cell and amplify the message.

• Typically, neurons do not touch each other. • If the chemical signal travels, say, from axon to dendrite, we call the nerve ends on the axon the presynaptic site. • The neurotransmitters are stored at the presynaptic site in vesicles, which are small, membrane-enclosed package. • Receptors are located on postsynaptic site of the cell body or the dendrite.

Jenis-jenis sinapsis a. Dendritik sinapsis ( dendritic synapse ) Sinapsis jenis ini terbentuk akibat bertemunya akson dari neuron pre-sinapsis dengan dendrit dari neuron post-sinapsis. b. Somatik sinapsis ( somatic synapse ) Sinapsis jenis terbentuk akibat bertemunya akson dari neuron pre-sinapsis dengan badan sel dari neuron post-sinapsis. c. Akson sinapsis ( axonal synapse ) Sinapsis jenis ini terbentuk akibat bertemunya akson dari neuron pre-sinapsis dengan akson dari neuron post-sinapsis.

Steps of Chemical Neurotransmission 1. Uptake of a precursor molecule 2. Synthesis of a transmitter within the cell 3. Storage of transmitter in vesicles 4. Release of transmitter into synaptic gap 5. Binding of transmitter to receptor sites on postsynaptic membrane 6. Message transmitted/Binding of transmitter to autoreceptors 7. Breakdown/reuptake of transmitter

Steps 1, 2, 3: The neurotransmitter is manufactured by the neuron and stored in vesicles at the axon terminal.

Step 4. When the action potential reaches the axon terminal, it causes the vesicles to release the neurotransmitter molecules into the synaptic cleft.

Step 5. The neurotransmitter diffuses across the cleft and binds to receptors on the post-synaptic cell. Step 6. The activated receptors cause changes in the activity of the post-synaptic neuron.

Step 7. The neurotransmitter molecules are released from the receptors and diffuse back into the synaptic cleft.

Step 7. The Neurotransmitter is re-absorbed by the post synaptic neuron. This process is known as Reuptake. Copyright 1997, Carlos G. Finlay and Michael R. Markham

Table of Neurotransmitters Transmitter Molecule Derived From Site of Synthesis Acetylcholine CNS, parasympathetic nerves Serotonin 5 -Hydroxytryptamine (5 -HT) Tryptophan CNS, chromaffin cells of the gut, enteric cells GABA Glutamate CNS Aspartate CNS Glycine spinal cord Histamine Histidine hypothalamus Epinephrine synthesis pathway Tyrosine adrenal medulla, some CNS cells Norpinephrine synthesis pathway Tyrosine CNS, sympathetic nerves Dopamine synthesis pathway Tyrosine CNS Adenosine ATP CNS, periperal nerves ATP Nitric oxide, NO sympathetic, sensory and enteric nerves Arginine CNS, gastrointestinal tract

REGULATION BY CHEMICAL MESSENGERS • ___________ released by neurons • ________ release by endocrine glands endocrine gland neurotransmitter axon hormone carried by blood receptor proteins target cell

• The distinction between hormones and neurotransmitters is physiological, not chemical. • Whether a certain compound is considered to be a neurotransmitter or a hormone depends on whether it acts over a short distance across a synapse (2 x 10 -6 cm), in which case it is a neurotransmitter. • Over a long distance (20 cm) from the secretory gland through the bloodstream to the target cell, in which case it is a hormone.

Hormone • Many organs in the body secreted biologically active compound called endocrine hormones, which are transported via blood stream to other tissues or organs where they exert a biological effect • As classically defined, is a substance that is synthesized in one organ and transported by the circulatory system to act on another tissue • Hormones can act on adjacent cells (paracrine) • Hormones can act on the cell in which they were synthesized without entering the systemic circulation (autocrine)

Hormone, a chemical messenger released by an endocrine gland into the bloodstream and transported there to reach its target cell

tropic hormones = target endocrine glands Hypothalamus thyroid-stimulating hormone (TSH) c Thyroid glandrticotropi oco H) adren one (ACT horm H) (G ne or mo th h L) PR n ( gonadotropic hormones: folliclestimulating hormone (FSH) & luteinizing hormone (LH) t me ocin lan oc yte -st cti ola gr ow Kidney tubules oxy pr Adrenal cortex antidiuretic hormone (ADH) posterior pituitary anterior pituitary im u Muscles of uterus lat ing ho rm (M one SH ) Melanocyte in amphibian Bone and muscle Testis Ovary Mammary glands in mammals

Effects of Hormones from the Pituitary Gland

Hormon • Pembawa pesan kimiawi. • Bersama saraf memadukan berbagai sistem organ (sistem koordinasi). • Zat - zat dengan aktivitas hormonal (protein, asam amino, asam lemak, steroid).

Struktur dasar hormon secara kimiawi : • Derivat asam amino : dikeluarkan oleh sel kelenjar buntu yang berasal dari jaringan nervus medulla suprarenal dan neurohipofise, contoh epinefrin dan norepinefrin. • Peptide /derivat peptide : dibuat oleh kelenjar buntu yang berasal dari jaringan alat pencernaan. • Steroid : dibuat oleh kelenjar buntu yang berasal dari mesotelium, contoh hormon testes, ovarium dan korteks suprarenal. • Asam lemak : merupakan biosintesis dari dua FA, contoh hormon prostaglandin.

Ø CIRI UMUM KELENJAR DUA SISTEM KELENJAR 1. KEL. EKSOKRIN Mengeluarkan sekresi melalui saluran (duktus) • Kel. Keringat • Kel. Lemak • Kel. Sistem Pencernaan

2. KEL. ENDROKIN ( KEL. BUNTU) Tidak mempunyai saluran. Sekresi → ke dalam sistem pembuluh darah Hormon adalah senyawa yang dihasilkan -mempunyai target organ -target organ mempunyai reseptor -target organ biasanya jauh dari tempat disintesis

DEFINITION OF HORMONE A chemical substance secreted by an endocrine gland or group of endocrine cells that acts to control or regulate specific physiological processes, including growth, metabolism, and reproduction. Most hormones are secreted by endocrine cells in one part of the body and then transported by the blood to their target site of action in another part, though some hormones act only in the region in which they are secreted.

MEKANISME KERJA HORMON Sekresi endokrin Sel endokrin mensekresi hormon→ hormon dialirkan ke darah → ditangkap oleh reseptor pada sel sasaran

Neurosekresi Badan sel saraf mensekresi hormon→ melalui akson hormon dialirkan melalui aliran darah → hormon ditangkap oleh reseptor pada sel sasaran

Neurotransmisi Badan sel saraf mengeluarkan sinyal → sehingga mempengaruhi sel sasaran melakukan sesuatu

Gland Hormone Ovary Graafian Follicle Estrogens (Estradiol) Inhibin (Folliculostatin) Chemical Principal Functions Class Steroid Protein Mating behavoir, Secondary sex characteristics, Maintenance of female duct system , Mammary growth Regulates release of FSH from anterior pituitary Corpus Luteum Progestins (Progesterone) Steroid Polypeptide Expansion of pelvis Dilation of cervix Relaxin Maintenance of pregnancy, Mammary growth & secretion

Testis Leydig Cells Androgens (Testosterone) Steroid Male mating behavior, Spermatocytogenesis, Maintenance of male duct system & accessory glands Regulates release of FSH Sertoli Cells Inhibin Protein Adrenal Cortex Glucocorticoids (Cortisol) Steroid Induction of partruition by fetus Milk synthesis Stress response Placenta Human Chorionic Gonadotropin (HCG) Glycoprotein Endometrial Cups Mare Equine Chorionic Gonadotropin (e. CG) Old name - Pregnant Mare Serum Gonadotropin (PMSG) Glycoprotein LH-like - Involved with establishment of pregnancy in human. Support and maintain CL FSH-like- some LH activity Immunological protection of foal during pregnancy Formation of accessory CL in mare Estrogens/Progestins Steroids Regulate placental bloodflow Maintenance of pregnancy Relaxin Protein Placenal Lactogen Glycoprotein Relaxation/dialation of cervix for parturition Stimulates mammary growth & milk secretion

Uterine Endometrium Graafian Follicles Seminal Vesicles Prostaglandin F 2 a (PGF 2 a) Lipid Liver Insulin-like Growth Factors IGF-I & IGF-II Protein Pineal Gland Melatonin Biogenic amine Posterior Pituitary Oxytocin Octapeptide Regression of CL , Stimulate myometrial contractions Ovulation Sperm transport Stimulates steroidogenesis, Stimulates mammary growth and fetal development Control of seasonal reproduction in Mare & Ewe Regulate hair growth Stimulate myometrial contractions for sperm transport, parturition & milk ejection

Anterior Pituitary Follicle Stimulating Glycoprotein Stimulate follicle growth Hormone (FSH) - Stimulate estrogen production Follicotropin Spermiogenesis in male Luteinizing Hormone (LH) - Luteotropin Glycoprotein Stimulate ovulation Support CL formation, and progesterone secretion Stimulate testosterone synthesis by leydig cells of testis Prolactin Protein Adrenalcorticotropi Protein c Hormone (ACTH) Stimulate milk synthesis Regulate metabolism for milk synthesis Effects Maternal Behavior Release of corticosteroids & glucocorticoids from adrenal cortex to initiate parturition

Hypothalamus Gonadotropic Releasing Decapeptide Hormone (Gn. RH) Dopamine Biogenic Amine Inhibits release of prolactin TRH Peptide PIF Stimulates release of FSH and LH from anterior pituitary Stimulates release of TSH Inhibits released prolactin Corticotropic Releasing Hormone (CRH) Peptide Stimulates ACTH release Growth Hormone. Releasing Hormone (GRH) Peptide Stimulates release of growth hormone Oxytocin Octapeptide Stimulates uterine contraction Partrus, transport of sperm and ova, Stimulates milk let down