Talk:BGD Lecture - Endocrine Histology

A Portal Circulation from the Pituitary to the Hypothalamic Region

Popa G. J Anat. 1930 Oct;65(Pt 1):88-91. No abstract available. First description of portal circulation

PMID 17104309

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1249186/

PARS DISTALIS . The pars distalis is composed of two general cell types: chromophils (50%) and chromophobes (50%). The chromophils can be further subdivided into acidophils (40%) and basophils (10%). The acidophils secrete GH (somatotropes) and prolactin (mammotropes). Basophils secrete TSH (thyrotropes), LH (gonadotropes), FSH (gonadotropes), and ACTH (corticotropes). The different acidophils and basophils cannot be distinguished in the light microscope. Chromophobes are undifferentiated or resting chromophils that appear weakly stained with smaller nuclei and less distinct borders. Observe the numerous blood vessels , the delicate connective tissue framework , and the connective tissue capsule . Recall that the hypophyseal portal circulation carries releasing hormones from the hypothalamus to the adenohypophysis targeting the acidophils and basophils and causing release of hormones into the blood stream.

PARS NERVOSA . Nerve fibers fill most of the pars nervosa but they are not easily identifiable without special stains. Note that the main cell type here is a glial or supporting cell called a pituicyte . The bulk of the pars nervosa consists of axons from neurons in the supraoptic and paraventricular nuclei of the hypothalamus. A few Herring Bodies are present. These are the storage sites of the neurosecretory material of the pars nervosa neurons. The Herring Bodies are identified as amorphous rounded eosinophilic bodies approximately the size of the smallest nuclei in the slide.

PARS INTERMEDIA . This structure (rudimentary in humans) lies between the pars distalis and pars nervosa. It consists mainly of colloid filled cysts lined by cuboidal epithelium. Note: a lumen may be present between the pars intermedia and pars distalis.

Endocrinology - An Integrated Approach

Stephen Nussey and Saffron Whitehead.

St. George's Hospital Medical School, London, UK Oxford: BIOS Scientific Publishers; 2001. ISBN-10: 1-85996-252-1

http://www.ncbi.nlm.nih.gov/books/NBK22/

Chapter 7. The pituitary gland

Chapter 4. The adrenal gland

Ghrelin immunoexpression in the human hypophysis

Appl Immunohistochem Mol Morphol. 2012 Jan;20(1):77-81.

Rotondo F, Rotondo A, Scheithauer BW, Cusimano M, Latta E, Syro LV, Kovacs K. Source Division of Pathology, Department of Laboratory Medicine, St. Michael's Hospital, University of Toronto, Toronto, Canada. rotondof@smh.ca Abstract The aim of this study was to immunohistochemically localize ghrelin in autopsy-obtained, nontumoral human pituitaries. Double immunostaining was also undertaken to determine the pituitary cell type expressing both adenohypophysial hormones and ghrelin. Results showed that ghrelin is present in the adenohypophysis, its immunoexpression being cytoplasmic, weak-to-moderate, and localized to a subset of cells. Double immunostaining showed that ghrelin is present in 51% to 90% of growth hormone-producing, luteinizing-producing, and α-subunit-producing cells. Ghrelin immunoexpression was less frequently observed in other adenohypophysial cell types, being seen in 30% of adrenocorticotropin and follicle-stimulating hormones, 15% of thyrotropin, and 10% of prolactin-immunoreactive cells. Ghrelin immunopositivity was also seen in nerve fibers and Herring bodies of the neurohypophysis and pituitary stalk. More work is needed to elucidate the role of ghrelin in adenohypophysial and neurohypophysial endocrine activity. It may well be that ghrelin exerts an autocrine/paracrine effect and can modulate hormone synthesis and release.

PMID 22157058

The role of lipotropins as hematopoietic factors and their potential therapeutic use

Exp Hematol. 2008 Jun;36(6):752-4. Epub 2008 Mar 20.

Halabe Bucay A. Source Department of Pediatrics, Hospital Angeles Lomas, Huixquilucan, Mexico. doctorhalabe@hotmail.com Abstract Lipotropins are peptides that act as hormones that are released from a common precursor together with other physiologically important peptides; their function is to mobilize the lipids that are stored in adipocytes as an energy reserve. This review will explain the existing scientific evidence on the action of lipotropins in adipocytes and, specifically, when these lipotropins activate bone marrow adipocytes to function as hematopoietic factors and suggest the potential therapeutic use of lipotropins based on these effects.

PMID 18358591

Anorexia nervosa: a unified neurological perspective

Int J Med Sci. 2011;8(8):679-703. Epub 2011 Oct 22.

Hasan TF, Hasan H. Source Mahatma Gandhi Mission's Medical College, Aurangabad, Maharashtra, India. zainabhasan52@hotmail.com

Abstract

The roles of corticotrophin-releasing factor (CRF), opioid peptides, leptin and ghrelin in anorexia nervosa (AN) were discussed in this paper. CRF is the key mediator of the hypothalamo-pituitary-adrenal (HPA) axis and also acts at various other parts of the brain, such as the limbic system and the peripheral nervous system. CRF action is mediated through the CRF1 and CRF2 receptors, with both HPA axis-dependent and HPA axis-independent actions, where the latter shows nil involvement of the autonomic nervous system. CRF1 receptors mediate both the HPA axis-dependent and independent pathways through CRF, while the CRF2 receptors exclusively mediate the HPA axis-independent pathways through urocortin. Opioid peptides are involved in the adaptation and regulation of energy intake and utilization through reward-related behavior. Opioids play a role in the addictive component of AN, as described by the "auto-addiction opioids theory". Their interactions have demonstrated the psychological aspect of AN and have shown to prevent the functioning of the physiological homeostasis. Important opioids involved are β-lipotropin, β-endorphin and dynorphin, which interact with both µ and κ opioids receptors to regulate reward-mediated behavior and describe the higher incidence of AN seen in females. Moreover, ghrelin is known as the "hunger" hormone and helps stimulate growth hormone (GH) and hepatic insulin-like-growth-factor-1(IGF-1), maintaining anabolism and preserving a lean body mass. In AN, high levels of GH due to GH resistance along with low levels of IGF-1 are observed. Leptin plays a role in suppressing appetite through the inhibition of neuropeptide Y gene. Moreover, the CRF, opioid, leptin and ghrelin mechanisms operate collectively at the HPA axis and express the physiological and psychological components of AN. Fear conditioning is an intricate learning process occurring at the level of the hippocampus, amygdala, lateral septum and the dorsal raphe by involving three distinct pathways, the HPA axis-independent pathway, hypercortisolemia and ghrelin. Opioids mediate CRF through noradrenergic stimulation in association with the locus coeruleus. Furthermore, CRF's inhibitory effect on gonadotropin releasing hormone can be further explained by the direct relationship seen between CRF and opioids. Low levels of gonadotropin have been demonstrated in AN where only estrogen has shown to mediate energy intake. In addition, estrogen is involved in regulating µ receptor concentrations, but in turn both CRF and opioids regulate estrogen. Moreover, opioids and leptin are both an effect of AN, while many studies have demonstrated a causal relationship between CRF and anorexic behavior. Moreover, leptin, estrogen and ghrelin play a role as predictors of survival in starvation. Since both leptin and estrogen are associated with higher levels of bone marrow fat they represent a longer survival than those who favor the ghrelin pathway. Future studies should consider cohort studies involving prepubertal males and females with high CRF. This would help prevent the extrapolation of results from studies on mice and draw more meaningful conclusions in humans. Studies should also consider these mechanisms in post-AN patients, as well as look into what predisposes certain individuals to develop AN. Finally, due to its complex pathogenesis the treatment of AN should focus on both the pharmacological and behavioral perspectives.

PMID 22135615

In search of HPA axis dysregulation in child and adolescent depression

Clin Child Fam Psychol Rev. 2011 Jun;14(2):135-60.

Guerry JD, Hastings PD. Source University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. jguerry@email.unc.edu

Abstract

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in adults with major depressive disorder is among the most consistent and robust biological findings in psychiatry. Given the importance of the adolescent transition to the development and recurrence of depressive phenomena over the lifespan, it is important to have an integrative perspective on research investigating the various components of HPA axis functioning among depressed young people. The present narrative review synthesizes evidence from the following five categories of studies conducted with children and adolescents: (1) those examining the HPA system's response to the dexamethasone suppression test (DST); (2) those assessing basal HPA axis functioning; (3) those administering corticotropin-releasing hormone (CRH) challenge; (4) those incorporating psychological probes of the HPA axis; and (5) those examining HPA axis functioning in children of depressed mothers. Evidence is generally consistent with models of developmental psychopathology that hypothesize that atypical HPA axis functioning precedes the emergence of clinical levels of depression and that the HPA axis becomes increasingly dysregulated from child to adult manifestations of depression. Multidisciplinary approaches and longitudinal research designs that extend across development are needed to more clearly and usefully elucidate the role of the HPA axis in depression.

PMID 21290178

Ultrastructural study of the human neurohypophysis. I. Neurosecretory axons and their dilatations in the pars nervosa

Cell Tissue Res. 1980;205(2):253-71. Seyama S, Pearl GS, Takei Y.

Abstract

Neurosecretory axons and their dilatations in the pars nervosa of the human neurohypophysis were studied electron microscopically. The axons are of two different types based on their content of neurosecretory granules (NSGs): (i) NSGs of Type A are 100-300 nm, and (ii) NSGs of type B are 50-100 nm in diameter. While fibers (or axons) of type B were scarce, showing simple swellings and terminal formations, fibers of type A were ubiquitous in the human pars nervosa, exhibiting numerous dilatations with a diversity of internal structure, apparently representing the ultrastructural manifestation of intraaxonal turnover of neurohypophysial hormones. Based on the predominating aspect of their internal structure, dilatations of type A-fibers were classified into six different types, with various transitional forms: Type I is characterized by abundant NSGs; type II by prominent mitochondria; type III by abundant lysosomal bodies; type IV by an electron-lucent matrix with few organelles; type V by prominent tubuloreticular profiles; and type VI by numerous microvesicles. The functional significance of each type is discussed and a scheme of possible interrelationships between these dilatations is proposed.

PMID 7357574

Practical 9: Histology of the Hypothalamic-Pituitary gland axis

Principal Teacher: Patrick de Permentier

Aim

To introduce students to neuro-endocrine relations by studying the histology of the hypothalamic– pituitary (HP) axis and some aspects of histopathology of the pituitary gland.

Specific Objectives:

To know the structure of the pituitary gland.
To understand the terms hypophysis; adenohypophysis; neurohypophysis; hypothalamohypophysial portal system.
To describe the parts of the adenohypophysis and to identify chromophilic cells (acidophils, basophils) and chromophobic cells of the pars distalis.
To know the structure of the neurohypophysis and the process of neurosecretion.
To know the histology of the adrenal gland.
To recognize some features of basic histopathology of the hypophysis.

Learning Activities

Pituitary gland (Human, Tri-PAS and Ox, Picro-Mallory)

At low magnification, identify the paler neurohypophysis consisting of pars nervosa (posterior lobe) and infundibulum (neural stalk). The nuclei scattered throughout the pars nervosa belong to cells called pituicytes, which are a type of neuroglial cell. Capillaries lined by elongated endothelial cells are present in the neurohypophysis.

The adenohypophysis is made up of pars distalis (anterior lobe), pars intermedia (intermediate lobe), and pars tuberalis (tuberal lobe that grows around the infundibulum). Note regional differences in staining of pars distalis that reflect regional differences in proportions of acidophils (intense magenta colour due to non-glycosylated proteins in cytoplasm), basophils (dark blue/purple cytoplasm due to the glycosylated proteins in cytoplasm) and chromophobes (do not take up dyes well). Note the colloid-containing follicles (Rathke’s cysts) in the pars intermedia; some follicles are lined by simple cuboidal/columnar epithelium derived from oral ectoderm. Basophils are more obvious in the pars intermedia (they sometimes grow in strands into the pars nervosa). capillaries are found in the adenohypophysis. Numerous sinusoidal

Hormones of human hypophysis
Chromophobes (50%)	Acidophils (40%)	Basophils (10%)
(ACTH); stem cells	GH; LTH (prolactin)	FSH; LH; MSH; TSH; ACTH

In the pars tuberalis, note the high density of venules packed with blood; these vessels belong to the hypothalamohypophysial portal system. Some thin arterioles with a pleated internal elastic lamina are also seen in this region.

The organ is surrounded by dense irregular connective tissue related to the dura mater. Connective tissue (reticular and collagen fibres) permeates the adenohypophysis and is very dense in the pars intermedia.

Pituitary gland

This slide is stained with H&E and shows similar features to the previous slides. The pink acidophils stand out but the difference between basophils and chromophobes. Herring bodies are seen occasionally in the more distal region of the pars nervosa. Some pituicytes in the pars nervosa aggregate in dense clusters.

Adrenal gland, primate – (Stain - Haematoxylin Eosin)

Identify the collagenous capsule and the cortical and medullary regions.

Within the cortex are 3 zones; namely Zona Glomerulosa (where the cells are arranged into ovoid groups and produce mineralocorticoids e.g. aldosterone increases sodium resorption from the glomerular filtrate by the kidney’s distal convoluted tubules), Zona Fasciculata (where cells are arranged into columns) and Zona Reticularis (bordering the medulla and cells forming cords). Both Zona Fasciculata and Zona Reticularis produce glucocorticoids of which cortisol is the most important by suppressing the immune system through arresting mitotic activities in the lymphoid tissues and decreasing the production of antibodies. These hormones are regulated by ACTH produced by the anterior pituitary gland.

As the adrenal gland is an endocrine structure, both the cortex and medulla have many capillaries (sinusoids) running between the cells. In the medulla many sinusoids drain into medullary veins. The cells in the medulla are the chromaffin cells with their granular appearance indicative of adrenalin and noradrenalin. The release of these hormones is under direct control of the ANS.