->One can remove endocrine glands and them replace the hormones to show a causal relationship between hormones and behavior.

->Hormones do not cause the behavior, but they increase or decrease the probability that the behavior occurs.

Research today focus on the specifics of what hormones are doing to produce their effects

-Where in the brain do they act?

-What genes are activated?

-What specific neural pathways mediate specific behaviors?

REVIEW the following basic concepts in

-biology of eucaryotic cells, genetic codes, secretary process

-neurobiology

-neuroendocrinology

-endocrinology

DEFINITIONS:

-Eucaryotic cells: cells containing a nucleus in which the genetic material is sequestered.

Chromosomes: fiber-like structures make up of DNA.

DNA: deoxyribonucleic acid, composed of 4 different nucleotides in a double strand that wraps around itself (the double helix). Codes for specific proteins but needs RNA to produce the proteins. DNA is used for template to produce a specific sequence of RNA inside the nucleus--> TRANSCRIPTION

RNA: ribonucleic acid, leaves the nucleus and enters the endoplasmic reticulum where the sequence of RNA molecules is translated into a protein--> TRANSLATION

CODON= a sequence of 3 RNA=code for 1 amino acid.

PROTEIN=sepcific sequences of amino acids

See figures 1.2, 1.3, 1.4 and 1.5 in your text.

Q: If all cells have the same DNA, why are cells in different parts of the body different?

A: Selective gene expression.

SELECTIVE GENE ACTIVATION OR REGULATION:

-> all cells contain the same genes. some cells only use a small percent of those genes, others use a lot more.

-> genes that are used are said to be expressed.

THE SECRETARY PROCESS

Cells communicate by the active process of releasing chemicals via EXOCYTOSIS. The chemicals that are released in this way are the neurotransmitters and the protein hormone. They are packaged into vesicles in the endoplasmic reticulum and Golgi apparatus and released into the extracellular space via a Ca++ dependent mechanism (See Fig. 1.4 ).

BASIC CONCEPTS IN NEUROBIOLOGY

Gross anatomy of the brain:

Telencephalon --- cortex: the lobes

--- limbic system

--- basal ganglia

Diencephalon ---- thalamus

---- hypothalamus

Mesencephalon --- tectum (roof)

--- Tegmentum

Metencephalon --- Pons, cerebellum

Myelencephlon --- medulla

Neurons are nucleated cells, thus they are eucaryotic cells.

Synaptic Transmission

->information (graded potentials) is received at cell body and dendrites, and summated at axon hillock.

->when input is sufficient to change membrane potential so that it is grater than threshold, an action potential is generated

->this results in synaptic transmission -- the release of neurotransmitter via exocytosis into synaptic cleft.

->neurotransmitter acts on receptors on postsynaptic neuron

->deactivation of neurotransmitter by degradative enzymes or removal by reuptake

To study how neurotransmitters work, scientists use various drugs to manipulate neurotransmitter systems

Agonist: drugs that mimic a neurotransmitter

Antagonist: drugs that block a neurotransmitter

Similar concepts apply to how hormones produce their effects in cells. (Fig. 1.9 and 1.10)

BASIC CONCEPTS IN NEUROENDOCRINOLOGY

In vertebrates, the hypothalamus is the "master gland" controlling the release of hormones from the anterior pituitary that act on target organs to produce peripheral hormone release from the adrenal gland, thyroid gland and gonads, as well as stimulation other bodily functions, mammary glands, and cell growth, etc. (an overhead showing the various endocrine organs highlighted in the human body and the hormones released form these glands, as well as the main functions of these hormones)

Specific hormones are released to promote specific functions. All are under feedback control.

We drew a graph showing the sagittal section of a rat and brain as well as an overhead of that of a human brain: the anatomical relationship of hypothalamus and pituitary gland.

An example of the negative feedback loop (overhead)

hypothalamus <-----------------|

| |

| TRH |

| |

V |

anterior pituitary <-------------|

| |

| TSH |

| |

V |

Thyroid gland-----> Thyroid hormones

We discussed in detail (chart on the board) the major hypothalamus-pituitary-endocrine gland axis, the specific hormones released, and the effects of these hormones. See figure 1.10, Table 1.4 for review.

There are two ways that the hypothalamus controls the hormonal secretion from the pituitary. The two distinct manners correspond with the anatomical organization of the anterior vs. posterior pituitary and their connections to the hypothalamus.

1. Hypothalamus affects anterior pituitary through the Releasing Hormones:

-> cell bodies of neurons that release the releasing hormones (GnRH, TRH, CRH, GRF) are located in specific hypothalamic nuclei

-> these neurons release the hormones into the blood system at the MEDIAL EMINENCE

-> These hormones them are carried by the blood to the anterior pituitary via hypophysial portal system. These hormones stimulate the anterior pituitary cells to secrete the Stimulating Hormones (FSH, LH, ACTH, TSH, PRL, etc.)

2. The other way occurs only for a couple of specialized neuronal populations that have their cell bodies in the hypothalamus, and extend axons into the posterior pituitary where they terminate close to blood vessels in the posterior pituitary. Neurons that make oxytocin or vasopressin, the two hormones we mentioned to be released from the posterior pituitary, use this strategy. They also have synapse in the brain, and communicate with other neurons.

BASIC CONCEPTS IN ENDOCRINOLOGY

Hormones can be categorized into two general classes according to their chemical structure:

STEROID HORMONES

-fat in composition

fat/lipid soluble

-hydrophobic (lipophillic)

-ready access to brain because they can cross the blood-brain barrier (BBB)

Hormones released by the gonads, adrenal cortex are steroid hormones. Thyroid hormones are made of amino acids, but they have steroid-like, 3-dimensional structures and behave like steroids, thus belong to this class (we made a chart showing the peptide hormones and the steroid hormones released from each endocrine gland).

We then showed the basic structure of steroids. All the steroid hormones are from a common precursor cholesterol, thus they are all related (also see Fig. 2.2).

cholesterol

|

V

progesterone ----> testosterone ---> estradiol

| |

V V

corticosterone dihydrotestosterone (DHT)

|

V

aldosterone

Q: How do these hormones affect brain and behavior?

A: Hormones interact with cells/neurons through specific receptor mechanisms.

Because of their chemical structures, the way they interact with cells is necessarily different, so we consider each class of hormones differently.

STEROID HORMONE RECEPTORS

-> steroid hormone can easily cross cell membranes and they do so.

-> enters cell and bind to INTRACELLULAR RECEPTORS

-> the steroid-receptor complex enters nucleus where it binds to acceptor site on DNA

-> DNA unwinds exposing a single strand

-> Transcription DNA --> RNA (RNA leaves cell nucleus)

-> Translation of RNA --> protein

-> Accumulation of protein can change cellular activity (e.g., it could synthesis more of its own receptors)

FEEDBACK REGULATION FOR STEROID RECEPTORS: UP-REGULATION

-> the system is primed by receiving its steroid hormone, there is an increase in the number of receptors.

-> With high concentrations of hormones there is decreed availability of receptors due to increased receptor occupancy. In addition, the rate of steroid receptor mediated response is decreased with low or constant hormone concentration.

KEY features of steroid receptors

- steroid hormone interact with intracellular receptors

- steroid hormones induce selective gene expression

- this effect is characterized as slow onset and long duration (hours to days; e.g., hormone treatment to ovariectomized female rats to induce sexual behavior during mating)

- steroid receptors are regulated by positive feedback mechanism

PEPTIDE /PROTEIN HORMONE RECEPTORS

-> peptide hormones are water soluble and cannot cross cell membranes

-> thus peptide hormones are bind to receptors located within the EXTRACELLULAR surface of cell membranes

-> Binding of the hormone to the receptor triggers a cascade events inside the cell:

-stimulates the activity of an enzyme

-promotes the formation of cAMP (second messenger)

-results in multiple biological responses

-> these receptor are very similar to the neurotransmitter receptors

FEEDBACK REGULATION FOR PEPTIDE RECEPTORS: DOWN-REGULATION

->High concentrations of peptide hormones decrease receptor sensitivity and number, as well as hormone release.

->Low concentrations of hormones results in increased receptor number and sensitivity (e.g., insulin independent type II diabetes)

KEY features of peptide hormone receptors

- peptide hormones interact with extracellular membrane bound receptors

- binding of the hormone to the receptor results in the activation of a second messenger system

- rapid effect (seconds to minutes)

- negative feedback regulation

The figures on your handout (hypothalamus and anterior pituitary vs. posterior pituitary; steroid receptor vs. peptide receptor mechanism) should give you a summary of what we have talked about today.