Hypothalamic Control of the Pituitary Gland Flashcards
The key to understanding the endocrine system is the concept of homeostasis.
a. There is continuing feedback and feed forward interaction between the various endocrine glands both by circulating levels of hormones as well as products of intermediary metabolism.
b. Multiple points of regulation allow subtle as well as large-scale manipulation of various endocrine functions but they also provide multiple points of dysfunction.
Hypothalamus
Large Summary
a. The hypothalamus forms the interphase between the brain and the endocrine system.
b. The connection between the anterior pituitary and the hypothalamus consists of a very specialized structure known as the hypothalamo-hypophyseal portal system.
c. Blood enters the median eminence through the superior hypophyseal arteries, which forms a capillary plexus.
i. Nerve terminals of appropriate hypothalamic neurons terminate here, (the capilllary plexus) and their neurohormones are released into this capillary bed and then are transported via the portal system vasculature to a second capillary plexus in the anterior lobe.
d. The ability of the plexus to have an easy access to the released hypothalamic hormones is because it lies outside the blood brain barrier.
e. Another consequence of this specialized structure is that hormones secreted by the involved hypothalamic neurons reach the anterior lobe relatively undiluted and thus at higher concentrations than would be achieved if they had been released into the general circulation.
f. Further, hypothalamic hormones act on a local rather than distant target.
i. If the portal system is severed or the anterior pituitary is transplanted elsewhere (where it may even become vascularized), secretion of anterior pituitary hormones will no longer be subject to normal hypothalamic control.
Hypothalamo-hypophyseal portal system
a. The connection between the anterior pituitary and the hypothalamus consists of a very specialized structure known as the hypothalamo-hypophyseal portal system.
b. Blood enters the median eminence through the superior hypophyseal arteries, which forms a capillary plexus.
c. Nerve terminals of appropriate hypothalamic neurons terminate at the capilllary plexus and their neurohormones are released into this capillary bed and then are transported via the portal system vasculature to a second capillary plexus in the anterior lobe.
d. Hypothalamic hormones are released into the capillary plexus in the median eminence and travel a relatively short distance, for a hormone, to the anterior pituitary.
i. Here, they regulate the secretion of hormones by the anterior pituitary into the general circulation.
Hypothalamo-hypophyseal portal system
Why its circulation is separate from the rest of the body
a. These two capillary plexus (the hypothalamic and anterior pituitary) are separate circulation from the rest of the body
b. Importance of isolated portal system: hormones secreted by hypothalamic neurons reach the anterior lobe relatively undiluted and thus at higher concentrations than would be achieved if they had been released into the general circulation.
c. Further, hypothalamic hormones act on a local rather than distant target.
i. If the portal system is severed or the anterior pituitary is transplanted elsewhere (where it may even become vascularized), secretion of anterior pituitary hormones will no longer be subject to normal hypothalamic control.
Hormones leaving the Hypothalamus and traveling to the Ant. Pituitary
a. Hypothalamic hormones are released into the capillary plexus in the median eminence and travel a relatively short distance, for a hormone, to the anterior pituitary.
b. Here, they regulate the secretion of hormones by the anterior pituitary into the general circulation.
c. The hypothalamic hormones are peptides, except for dopamine (DA), which is a catecholamine, and are usually considered in relation to the anterior pituitary hormone’s secretion that they influence.
Actual hormones released from Hypothalamus to Anterior Pituitary
- Thyrotropin releasing hormone (TRH)
i. tripeptide
ii. Ant Pit: Increase TSH; Increase PRL - Gonadotropin releasing hormone (GnRH)
i. decapeptide
ii. Ant Pit: Increases LH; Increases FSH - Corticotropin releasing hormone (CRH)
i. 41 amino acids
ii. Ant Pit: Increases POMC ; Increases ACTH - Growth hormone releasing factor (GHRH)
i. 14 amino acids
ii. Ant Pit: Increases GH - Somatostatin (GH inhibiting hormone; GIH)
i. 14 amino acids
ii. Ant Pit: decreases GH; decreases TSH - Prolactin inhibiting factor (PIH)
i. Dopamine (DA)
ii. Ant Pit: decreases PRL
Side notes of these hormones released from Hypothalamus to the Ant Pituitary
a. As suggested by the nomenclature, some of these hormones stimulate while others inhibit the secretion of hormones from the anterior pituitary.
i. In some cases, factors have been identified that stimulate and others that inhibit the secretion of the same hormone, e.g., GHRH and somatostatin stimulate and inhibit, respectively, the secretion of GH.
b. The hypothalamic hormones are peptides, except for dopamine (DA), which is a catecholamine, and are usually considered in relation to the anterior pituitary hormone’s secretion that they influence.
- Thyrotropin releasing hormone (TRH)
i. tripeptide
ii. Ant Pit: Increase TSH; Increase PRL - Gonadotropin releasing hormone (GnRH)
i. decapeptide
ii. Ant Pit: Increases LH; Increases FSH - Corticotropin releasing hormone (CRH)
i. 41 amino acids
ii. Ant Pit: Increases POMC ; Increases ACTH - Growth hormone releasing factor (GHRH)
i. 14 amino acids
ii. Ant Pit: Increases GH - Somatostatin (GH inhibiting hormone; GIH)
i. 14 amino acids
ii. Ant Pit: decreases GH; decreases TSH - Prolactin inhibiting factor (PIH)
i. Dopamine (DA)
ii. Ant Pit: decreases PRL
Hypothalamus Input
The hypothalamus receives inputs from the thalamus, limbic system including:
i. olfactory bulb, hippocampus, habenula and amygdala, the retina,
ii. reticular activating substance and the neocortex
iii. information regarding pain, sleep versus wakefulness, emotions, fright, rage, olfactory sensations
iv. light reaches the hypothalamus and can affect the activity of the neurosecretory neurons.
Stimulus-dependent secretion of the hypothalamus
a. Stimulus-dependent secretion of hypothalamic hormones occurs in a manner similar to neurotransmitter release.
b. In brief, appropriate stimulation of a hypothalamic neuron will result in generation of action potentials
c. At the nerve terminal, calcium entry through voltage-dependent calcium channels will lead to liberation of hormone (versus neurotransmitter) from secretory vesicles.
d. Thus, just as for neurotransmitter release, hormone secretion from hypothalamic neurons is calcium-dependent.
Cellular mechanisms of action of hypothalamic hormones:
a. At a cellular level, the hypothalamic hormones interact with specific receptors on their appropriate target cells in the anterior pituitary.
i. The intracellular signaling cascades are the subject of much current investigation.
b. One point of agreement is that extracellular calcium is required for the release.
i. Involvement of calcium release from intracellular stores is still debatable.
c. The hormones bind to their respective receptors, which in turn are coupled to various G-proteins.
i. CRH and GHRH receptors are coupled to Gs and, upon activation, stimulate adenylate cyclase to produce cAMP in corticotrophs and somatotrophs, respectively.
ii. In contrast, the interaction of somatostatin with Gi eventually leads to a decrease in cAMP.
iii. Similarly, DA leads to a reduction in cAMP levels in lactotrophs.
iv. CRH also leads to an increase in the rate of transcription of POMC and formation of ACTH.
Summary of Hypothalmic Hormone effect on the Anterior Pituitary
a. In sum, although release of hormone from anterior pituitary cells is dependent upon calcium, evidence exists implicating several intracellular signaling cascades to different degrees in the various pituitary cells.
b. Membrane conductances also appear to play a role.
c. These intracellular cascades are probably also involved in regulating the synthesis of various pituitary hormones.
The Pituitary Gland
Summary
a. The pituitary gland acts as an endocrine control center responding to neural signals, and catering to the needs of various target tissues (e.g.,thyroid, gonads, adrenal gland, bone), coordinating and regulating their functions.
b. The gland is attached to a region of the brain (hypothalamus) by a structure known as the pituitary stalk.
i. This anatomical connection is necessary for the functional interactions between the brain and pituitary.
c. The pituitary consists of two major divisions, the anterior (adenohypophysis) and the posterior hypophysis (neurohypophysis).
d. The anterior pituitary is derived from an embryological structure known as Rathke’s pouch (pharyngeal epithelium)
i. the intermediate pituitary is also found within the adenohypophysis, but is extremely small in humans and not thought to be of functional significance.
e. The posterior pituitary is derived from neural tissue arising from an embryological evagination of the diencephalon.
What the anterior and posterior pituitary come from
a. The anterior pituitary is derived from an embryological structure known as Rathke’s pouch (pharyngeal epithelium)
b. The posterior pituitary is derived from neural tissue arising from an embryological evagination of the diencephalon.
Adenohypophysis- the Anterior Pituitary gland
a. The anterior pituitary is comprised of the pars tuberalis, pars intermedia (intermediate lobe) and the pars distalis (anterior lobe).
i. We will focus on the anterior lobe/ pars distalis, since the hormones of the anterior pituitary are secreted from this structure.
b. Six hormones are released from the anterior lobe. Their secretion is under control of the hypothalamic hormones
1. TRH acts on cells called thyrotrophs to stimulate the secretion of TSH
2. GnRH acts on gonadotrophs to stimulate the secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH)
3. GHRH and somatostatin act on somatotrophs to stimulate and inhibit, respectively, the secretion of growth hormone (GH)
4. CRH acts on corticotrophs to stimulate the secretion of corticotropin (ACTH) and proopiomelanocortin (POMC);
5. prolactin inhibiting hormone (PIH, thought to be DA) and prolactin releasing factor (PRF, perhaps TRH?) act on mammotrophs to inhibit and stimulate, respectively, the secretion of prolactin (PRL).
Pulsatile Secretion and Endocrine Rhythms
a. The release of hormones from the anterior pituitary is not constant over time but instead is quite varied and described as pulsatile.
b. There are periods of higher release followed by periods of diminished release.
i. Thus, the plasma levels show spikes or pulses.
c. It may be that this type of secretion is directed by pulsatile secretion of the stimulating (or inhibiting) hypothalamic hormone.
i. Evidence for this mechanism is strong for LH, FSH (GnRH pulse generator) and ACTH.
d. Pulsatile, rather than continuous, secretion of hypothalamic hormones is the effective signal guaranteeing appropriate stimulation of the anterior pituitary.
