Hypothalamus as an Endocrine Gland
15.2.1 Introduction
The higher centres for regulating body temperature, appetite, sexual behaviour, sleep-wake cycle, and emotional states reside in the hypothalamus. In addition, it secretes various hormones with a wide range of afferent neural pathways, thereby playing a pivotal role in integrating nervous and endocrine systems.
These neurohormones further regulate the endocrine activities of the pituitary gland.Table 15.3 Different hypothalamic nuclei and their secretory hormones
| S. No | Hypothalamic nuclei | Hormone(s) |
| 1. | Para-ventricular nucleus (PVN) | CRH,GHIH,TRH,ADH |
| 2. | Pre-optic area (POA) | GnRH |
| 3. | Dorsomedial nucleus (DMN) | GnIH |
| 4. | Arcuate nucleus (ACN) | GHRH, DA (PIH) |
| 5. | Supra-optic nucleus (SON) | OT |
15.2.2 MechanismofSecretion
The hypothalamic hormones are synthesised by specialised neuroendocrine cells that are organised as distinct nuclei (Table 15.3). Magnocellular (MC) and parvocellular (PC) neurons are the two different categories of neuronal cells in hypothalamus that confer its neuroendocrine activity. The nerve terminals of MC neurons end in a specialised area known as median eminence. The parvocellular neurons are characterised by long axons that traverse through pituitary stalk reaching the posterior pituitary lobe, they are responsible for secreting anti-diuretic hormone (ADH) and oxytocin (OT). Hence, ADH and OT are commonly categorised as posterior pituitary hormones.
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• Although oxytocin is mainly synthesised in SON, it is also produced in little quantities from PVN. In the same way, SON acts as a minor source of ADH.
• Popa and fielding were the first to describe about “Hypophyseal portal system”.
15.2.3 Hypothalamic-Hypophyseal Portal (HHP) System
The median eminence is the site of origin for “hypothalamic-hypophyseal portal system”. The portal system consists of a hypophyseal artery derived primary capillary bed, which embeds median eminence, and a secondary capillary bed formed from the long portal veins in the anterior pituitary lobe. This acts as a functional connecting circuit between the hypothalamus and anterior lobe of pituitary (Fig. 15.8).
15.2.4 HypothalamicHormones
The hypothalamic hormones released by MC nerve terminals located in the median eminence are carried by the HHP system to act on their target cells in the pituitary gland. With the pituitary gland as their only target organ, they act on different neuronal cell types to either stimulate or inhibit its endocrine activity. Therefore, the hypothalamic hormones are broadly categorised as releasing and inhibiting hormones based on their effect on pituitary gland.
15.2.4.1 MechanismofAction
They act by binding to their respective GPCRs, result in either stimulation or inhibition of adenylyl cyclase (AC) or phospholipase C (PLC) systems. This results in affecting the levels secondary messengers, initiating various downstream signalling pathways to either produce or inhibit synthesis and secretion of pituitary hormones (Table 15.4).
Fig. 15.8 Hypothalamic- hypophyseal portal system. [Hypothalamic hormones released in median eminence enter the hypophyseal portal system and stimulate the neuroendocrine cells in the anterior pituitary to release tropic hormones into the systemic circulation. [MC magnocellular neuron; PC parvocellular neurons; OT oxytocin; ADH anti-diuretic hormone]
Table 15.4 List of hypothalamic hormones, their respective chemical structure, mechanism of action and function [" = increase, # = decrease]
| S. No | Hormone | Chemical structure | Target cell | Mechanism of action | Target effect |
| 1. | Thyrotropin-releasing hormone (TRH) | Peptide (3 a.a) | Thyrotropes | Stimulate phospholipase C system ( "DAG & IP3) | Stimulate TSH secretion |
| 2. | Corticotropin-releasing hormone (CRH) | Peptide (41 a.a) | Corticotropes | Stimulate adenylyl cyclase system ("cAMP) | Stimulate ACTH secretion |
| 3. | Gonadotropin-releasing hormone (GnRH) | Peptide (10 a.a) | Gonadotropes | Stimulate phospholipase C system ("DAG & IP3) | Stimulate gonadotropins (LH &FSH) secretion |
| 4. | Growth hormone-releasing hormone (GHRH/Somatocrinin) | Peptide (44 a.a) | Somatotropes | Stimulate phospholipase C system ("DAG & IP3) | Stimulate GH secretion |
| 5. | Gonadotropin-inhibiting hormone (GnIH) | Peptide (12 a.a) | Gonadotropes | Inhibit adenylyl cyclase system QcAMP) | Inhibit Gonadotropin secretion |
| 6. | Growth hormone inhibitory hormone (GHIH/Somatostatin) | Peptide (14 a.a) | Somatotropes | Inhibit adenylyl cyclase system QcAMP) | Inhibit GH secretion |
| 7. | Prolactin inhibiting hormone (PIH/Dopamine) | Tyrosine derivative | Lactotropes | Inhibit adenylyl cyclase system QcAMP) | bgcolor=white>Inhibit PRL secretion
15.2.4.2 Regulation of Secretion
Pituitary tropic hormones and their target hormones regulate the secretion of hypothalamic hormones.
From systemic circulation, they can enter the brain via fenestrated capillaries found in circum-ventricular organs or choroid plexus into cerebrospinal fluid (CSF). These factors then act directly or indirectly on the neuroendocrine cells of hypothalamus and modulate their secretions.Know More...
• The hypophyseal portal system prevents the entry of hypothalamic hormones into the systemic circulation. It helps in rapid delivery of hormones to the pituitary gland without being diluted. Hence, their concentration cannot be measured in the general circulation.
• Kisspeptin, a neuropeptide that acts on GnRH producing neurons plays major role in the onset of puberty and modulating hypothalamo-pituitary- gonadal (HPG) axis. Currently, it is being used to advance puberty and to develop novel oestrus synchronisation protocols in animals.
• GnIH was first identified in Japanese quail.
15.3