Pars intermedia

Ciliated cells are occasionally found in the junctional zone between pars intermedia and pars nervosa of the rat pituitary particularly in association with the ramifications of the pituitary cleft (Howe and Maxwell 1968). 

The cells in the pars intermedia of the rat pituitary produce a series of biologically active peptides, i.e., a-melanocyte-stimulating hormone, CLIP, p-endorphin, P-hpotropin, and y-MSH-related peptides. The pro-opiomelanocortin-derived peptides, especially a-MSH and P-endorphin, are suggested to be involved in learning and memory (O Dono- 

Granular cells Melanotrophs Corticotrophs PAS-positive cells Agranular cells Cleft cells 

Folliculo-stellate cells Bordering or marginal cells 

Miscellaneous cell types Fibroblasts Eosinophil leucocytes Mast cells 

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The pituitary gland is situated in sella turcica or hypophyseal fossa of the sphenoid bone attached to the brain by a stalk which is continuous with the part of brain i.e. hypothalamus and there is a communication between the hypothalamus and the pituitary gland by means of nerve fibres and a complex of blood vessels. Pituitary gland consists of three parts - anterior lobe or adenohypophysis, posterior lobe or neurohypophysis and middle lobe or pars intermedia. 

Connected to the brain by a stalk (Fig. 30-1), the pituitary gland releases at least ten peptide or protein hormones that regulate the activity of other endocrine (hormone-producing) glands in distant parts of the body. The pituitary is composed of several distinct parts the anterior lobe (adenohypophysis), a thin intermediate portion (pars intermedia), and a posterior lobe (neurohypophysis). Each has its own characteristic endocrine functions. 

Pituitary Hormones. The hormones of the hypophysis (pituitary gland) are quite numerous, being secreted variously in three parts of the gland — the ncurohypophysis (posterior lobel. the adenohypophysis (anterior lithe), and the pars intermedia, which connects the other two. 

The chief hormones of the iteurohypophysis are the polypeptides oxytocin and vasopressin. The hormone characteristic of the pars intermedia Is the melanocyte-stimulating hormone. It is usually spoken of in the plural, since in most mammals both alpha and beta forms are known. The structures of the liist two arc shown In the Table I. The most prominent effect of oxytocin is the contraction ot smooth muscle, especially of the uterus, It also has a major effect upon the muscles about ihe breast, and so stimulates the ejection of milk in I,totaling animals. It has a delinile stimulating effect upon (he muscles of Ihe ureter, urinary bladder, intestine, and gall bladder. 

Triphenyltin hydroxide caused dose-related cystoid changes in the pars intermedia of the pituitary gland for male and female mice administered this compound for 52 or 104 weeks at doses of 0.3-6.2 mg/kg/day (Tennekes et al. 1989a). Up to 40% of the males and 80% of the females were affected at 52 weeks by the highest dose. At the end of 104 weeks, 72.3% of the high dose males and 55.6% of the females exhibited the cystoid changes. The lower incidence in females at 104 weeks related to a high early mortality from fatal pituitary adenomas (see Section 2.2.2.8). 

As illustrated in Fig. 3A, dopamine leads to a 30% (p <0.01) inhibition of basal cyclic AMP levels in pars intermedia cells at an EDgg value of 5.0 nM. An almost identical potency of dopamine is observed on the elevated cyclic AMP concentration induced by simultaneous incubation with 30 nM (-)isoproterenol (Fig. 3B). Similar inhibitory effects of dopamine are observed in the presence of a phosphodiesterase inhibitor, isobutylmethylxanthine, thus... 

Figure 3. Effect of increasing concentrations of dopamine on basal (A) and (—fisoproterenol-induced (B) cyclic AMP levels in rat pars intermedia cells in culture. Cells were incubated for 30 min in DMEM containing 5 mM HEPES, 100 pM ascorbic acid, and the indicated concentrations of dopamine alone (A). In B, 30 nM (—(isoproterenol was present during the last 4 min of incubation. Data are expressed as percent of control (in the absence of dopamine). Control cyclic AMP levels were 0.96 0.10 and 5.29 0.13 pmol/2 X 10s cells in the absence (A) or presence (B) of 30 M (—(isoproterenol, respectively (41).

After a 6-h incubation with pars intermedia cells in culture, a maximal concentration of ovine CRF (300 nM) causes a 2-fold stimulation of a-MSH release at an ED5Q value of 1 nM (Fig. 5B). 

In rat pars intermedia cells, the rate of secretion of the proopiomelanocortin-derived peptides (a-MSH being the major secretory product) (3, 85) was so far known to result from a balance between the stimulatory effect of B-adrenergic agents and the inhibitory influence of dopaminergic substances (14, 41, 86-89). The present data clearly demonstrate that in addition to B-adrenergic agents, a second substance, namely CRF, could well be involved as physiological stimulator of the activity of pars intermedia cells. 

Since the adenylate cyclase system has been well demonstrated to play a mediatory role in controlling the action of B-adrenergic and dopaminergic agents in pars intermedia cells (5-13, 41), we have studied the possibility of a similar role of cyclic AMP in CRF action. After a 10-min incubation with increasing CRF concentrations, an approximately 6-fold increase in cyclic AMP content is measured at an ED q value of 6 nM (Fig. 5A). A maximal stimulatory effect of CRF on cyclic AMP accumulation is observed 2 min after addition of CRF. As observed on a-MSH secretion, preincuba-... 

Figure 5. Effect of increasing concentrations of CRF on cyclic AMP content (A) and a-MSH release (B) in rat pars intermedia cells in culture. After 5 d in culture, cyclic AMP content and a-MSH release were measured after 10 min and 6 h of incubation, respectively, with the indicated concentrations of CRF. Dexamethasone (100 nM) was present for 24 h in the appropriate...

The above-described data show that CRF added to cells of the rat Intermediate lobe In culture causes a rapid stimulation of oe-MSH release and cyclic AMP accumulation, thus demonstrating a direct action of the peptide on pars intermedia cells (15). It is however difficult, using intact cells, to dissociate between increases in cyclic AMP levels due to stimulation of adenylate cyclase activity or to Inhibition of cyclic nucleotide phosphodiesterase or to a combination of both effects. Definitive proof of the role of adenylate cyclase In the action of CRF In the intermediate lobe of the pituitary gland is provided by the following findings of a CRF-lnduced stimulation of adenylate cyclase activity in homogenate of rat and bovine pars Intermedia cells. 

As Illustrated in Fig. 7, 3 yM CRF and 1 yM (-)Isoproterenol cause a 190 and 110% stimulation of adenylate cyclase activity In rat pars intermedia particulate fraction, respectively. An additive effect Is observed when both stimulatory agents are present. Dopamine (30 yM), on the other hand, has no significant effect alone. However, In the presence of GXP, the catecholamine causes a 40 to 60% Inhibition of adenylate cyclase activity stimulated by CRF, ISO or CRF + ISO. It can also be seen that while 0.3 mM GXP alone causes a 100% increase In basal adenylate cyclase activity, it leads to a marked potentiation of the effect of ISO and CRF on [ 2P] cyclic AMP accumulation. It should be noticed that In the absence of the guanyl nucleotide, dopamine has no Inhibitory effect on adenylate cyclase activity In any of the groups studied. 

The present data clearly demonstrate that the 41-amino acid ovine CRF Is a potent stimulator of adenylate cyclase activity In rat and bovine pars Intermedia tissue. Our previous data have shown that CRF causes a rapid and marked stimulation of cyclic AMP accumulation in rat pars Intermedia cells in culture (15). The final proof of the role of adenylate cyclase in the observed changes of cyclic AMP levels had to be obtained by direct measurement of adenylate cyclase activity. 

As mentioned earlier, guanyl nucleotides have been found to play an important role In the activation of adenylate cyclase activity by many hormones (90, 91). The present observations show that in pars Intermedia tissue, GXP causes an almost doubling of the stimulatory effect of CRF while that of the B-adrenerglc ago-... 

Figure 6. Effect of increasing concentrations of CRF on adenylate cyclase activity in bovine pars intermedia pituitary homogenate.

Figure 8. Representation of the interaction between CRF, -adrenergic, and dopaminergic (DA.) receptors in the control of pars intermedia cell activity. The CRF and / -adrenergic receptors stimulate adenylate cyclase activity through interaction with the Ns-GTP-binding component. Dopamine, on the other hand, interacts with the Ni-GTP-binding component, causing inhibition of basal as well as CRF- and f3-adrenergic-induced adenylate cyclase activity.

Williams PJ, MacVicar BA, Pittman QJ (1990) Synaptic modulation by dopamine of calcium currents in rat pars intermedia. J Neurosci 70 757-763. 

David MD (1986) The hypothalamo-hypophyseal rat explant in vitro endocrinological studies of the pars intermedia dopaminergic neural input. J Physiol 370 381-393. 

Meunier H, Labrie F (1982) Beta-adrenergic, CRF-ergic and dopaminergic mechanisms controlling a-MSH secretion in rat pars intermedia cells in primary cell culture. Prog Neuropsychopharmacol <5 411 115. 

ECD is nearly always associated with hypertrophy, adenomatous h3q>erplasia or, in the most advanced cases, a functional adenoma of the pars intermedia of the pituitary gland. This condition was first described in 1932 however the exact pathogenesis, diagnostic plan and appropriate treatment regimen are still under dispute. Although, all breeds of horses and both sexes... 

A diagnosis of ECD is usually confirmed by testing the pituitary-adrenal axis. Single or multiple measurements of plasma cortisol are not diagnostic for ECD. In fact, cortisol concentrations vary widely in normal horses and the values from horses with pars intermedia dysfunction are often within the reference range (Dybdal et al 1994). Additionally, cortisol concentrations may be... 

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