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Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

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I. Hypothalamus-Pituitary System<br />

565<br />

organization <strong>of</strong> cytoplasmic organelles for peptide synthesis<br />

and release. Characteristics such as the form, size, and<br />

location <strong>of</strong> the various organelles and the size and shape<br />

<strong>of</strong> the cells and their nuclei allow identification <strong>of</strong> adenohypophyseal<br />

cells at the ultrastructural level ( Batten and<br />

Ingleton, 1987 ; Mikami, 1986 ).<br />

The distribution <strong>of</strong> the various secretory cells <strong>of</strong> the AL<br />

is not random, different hormone-secreting cells preferentially<br />

accumulate at different sites in the AL. This topological<br />

organization <strong>of</strong> the AL is well known in the human<br />

and may also be true for domestic animals. The gland comprises<br />

a central “ mucoid ” wedge containing thyrotropes<br />

and corticotropes and lateral wings containing somatotropes<br />

and lactotropes. The gonadotropes are distributed<br />

diffusely throughout the gland. Also, the numerical contribution<br />

<strong>of</strong> each AL cell type is not the same. In the pituitary<br />

anterior lobe <strong>of</strong> humans the distribution is corticotrope<br />

(10% to 15%), thyrotrope (5%), somatotrope (50%), lactotrope<br />

(10% to 30%), and gonadotrope (15% to 20%).<br />

The concept <strong>of</strong> one pituitary cell making one hormone<br />

is an oversimplification. Immunoelectron microscopy has<br />

shown that one hormone can be produced by the same or different<br />

cell populations. In some instances, multiple hormones<br />

are produced by the same cell population and have even been<br />

visualized within the same secretory granule. The majority<br />

<strong>of</strong> gonadotropes and somatomammotropes is multihormonal<br />

cells that contain LH and FSH or GH and PRL, respectively.<br />

Also, other combinations such as gonadotroph hormones and<br />

ACTH or TSH and ACTH have been described.<br />

In addition to the functionally distinctive AL cell types<br />

noted above, cells termed “ stellate ” or “ folliculostellate ”<br />

also occur within the normal pituitary. Folliculostellate<br />

cells lack secretory granules as well as hormone secretion<br />

and are characterized by processes that insinuate themselves<br />

between the AL cells. The physiological role <strong>of</strong><br />

folliculostellate cells is uncertain. They are thought to be<br />

supportive in nature and synthesize a variety <strong>of</strong> chemical<br />

messengers, intrapituitary growth factors, and cytokines<br />

that exert local paracrine effects on cell function and proliferation<br />

( Denef, 1994 ).<br />

6 . Cells <strong>of</strong> the Intermediate Lobe (IL)<br />

The predominant IL cell in mammals is the melanotrope, a<br />

cell with immunoreactivity for α -MSH, which is sparse in<br />

the AL ( Halmi and Krieger, 1983 ). In some species, including<br />

the dog ( Halmi et al. , 1981 ) and the horse ( Amann<br />

et al. , 1987 ), the IL is cytologically heterogeneous. ACTHcontaining<br />

cells (B cells) have been found to be dispersed<br />

among the predominant melanotropes (A cells). In the dog,<br />

the immunoreactive ACTH content <strong>of</strong> the IL even exceeds<br />

that in the AL ( Halmi et al. , 1981 ). In ferrets, as in dogs<br />

and cats, the melanotropic cell was the most abundant cell<br />

type <strong>of</strong> the IL ( Schoemaker et al. , 2004 ). In agreement<br />

with the previously mentioned direct neural regulation <strong>of</strong><br />

IL secretory activity, the presence <strong>of</strong> neural elements was<br />

demonstrated in the bovine IL ( Boyd, 1987 ). Evidence is<br />

accumulating that the cells <strong>of</strong> the pars intermedia are also<br />

involved in the biosynthesis and release <strong>of</strong> a yet unknown<br />

prolactin-releasing factor. The blood supply <strong>of</strong> the IL is<br />

poor, and therefore the peptides released from the IL are<br />

thought to mainly act by diffusion in a paracrine manner.<br />

7 . Cells <strong>of</strong> the Neural Lobe (NL)<br />

The NL contains axonal nerve fibers, <strong>of</strong>ten swollen by<br />

being packed with neurosecretory granules. These nerve<br />

fibers and the glial cells (pituicytes) have synaptoid contacts.<br />

The pituicytes play an intermediary role in the regulation<br />

<strong>of</strong> the release <strong>of</strong> vasopressin and oxytocin ( Rosso<br />

et al. , 2004 ).<br />

B . Regulation <strong>of</strong> Pituitary Functions<br />

For the regulation <strong>of</strong> each <strong>of</strong> the five major adenohypophyseal<br />

hormone systems (ACTH, LH and FSH, TSH,<br />

GH, and PRL), there is a feedback (closed-loop) system.<br />

AL hormone and hypophysiotropic hormone secretions<br />

are suppressed by the products <strong>of</strong> target endocrine glands<br />

such as the thyroid, adrenals, and gonads. Apart from this<br />

long-loop feedback, some hormones (e.g., PRL) regulate<br />

their own secretion directly by acting on the hypothalamus<br />

(short-loop feedback). On this powerful feedback<br />

control with primarily blood-borne signals, other signals<br />

are superimposed. These may originate within the central<br />

nervous system (open loop) and can be mediated through<br />

neurotransmitters and hypophysiotropic hormones. Thus,<br />

influences are exerted that represent the environment<br />

(temperature, light-dark), stress (pain, fear), and intrinsic<br />

rhythmicity.<br />

These regulatory factors influence peptide synthesis or<br />

release in adenohypophyseal cells, where each <strong>of</strong> the steps<br />

in hormone synthesis and ultimate secretion represents a<br />

potential control point in the regulation <strong>of</strong> circulating hormone<br />

concentrations.<br />

1 . Hypophysiotropic Hormones<br />

The main hypothalamic neurohormones may stimulate or<br />

inhibit the release <strong>of</strong> a single hormone, or it may affect several<br />

hormone-producing cells ( Fig. 18-3 ). The predominant<br />

influence <strong>of</strong> the hypothalamic hormones on the pituitary is<br />

stimulatory, and these peptides are known as releasing hormones<br />

( Guillemin, 2005 ). Interference with the integrity <strong>of</strong><br />

the hypothalamic-pituitary connections results in decreased<br />

secretion <strong>of</strong> pituitary hormones. The exception is PRL, the<br />

secretion <strong>of</strong> which is increased when hypothalamic influence<br />

is removed.<br />

As the complexity <strong>of</strong> the peptide structures <strong>of</strong> the hypophysiotropic<br />

hormones increases, species variation in

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