Early Postnatal Development of Pituitary Intermediate Lobe Control in the Rat by Dopamine Neurons

Abstract

In fetal and postnatal rats, serum melanophore-stimulating hormone (MSH) levels, pituitary ³H-spiperone binding, pituitary catecholamine content, and other parameters were measured to characterize the development of pars intermedia pituitary control by the tubero-hypophyseal dopamine system. Bioassay of serum for MSH revealed low but significant levels 6 days before birth (gestational day 17), rising to a peak 4 days after birth (postnatal day 5). Levels declined after PN 6, reached a low 2 weeks after birth, and then rose gradually throughout the next several weeks until adult values were attained. From excised pituitaries, significant catecholamine fluorescence in the neurointermediate lobe was first demonstrated on the 2nd postnatal day, with the highest density of fibers being attained at 2 weeks after birth. Thereafter, the density of terminals decreased in the pars intermedia until the adult pattern of innervation was observed at day 60. Total dopamine content of the neurointermediate lobe roughly paralleled the morphological observations through the first 2 weeks after birth. Later, content was seen to stabilize, while concentration decreased in line with the reduction in terminal density. Dopamine levels exceeded norepinephrine concentration by a factor of 10. ³H-spiperone binding sites were present in the pituitary before birth. Their density increased rapidly in the neurointermediate lobe during the first 2 postnatal weeks, then diminished until adult densities were reached at day 30. Binding in the anterior pituitary slowly rose throughout the first 30 days after birth, although values were only about one-quarter of that found in the neurointermediate lobe. In vitro incubation of neurointermediate lobes with dopamine showed a dose-dependent inhibition of spontaneous MSH secretion as early as 2 days after birth. Blockade of dopaminergic binding sites by i.p. administration of cis-flupenthixol (1 mg/kg) to rat pups had no effect until days 8, 15, and 22 where there was a significant rise in serum MSH levels as compared with controls. These data indicate that the intermediate lobe is responsive to dopamine at around birth, while the inhibitory dopaminergic control develops only during the 1st postnatal week, in conjunction with marked changes in circulating MSH levels.

The hypothalamo‐hypophyseal rat explant in vitro: endocrinological studies of the pars intermedia dopaminergic neural input.

“…In addition, the evidence demonstrates that the tubero-hypophyseal dopamine system has already reached a significant level of development in explants taken from the 2-week-old rats used in this study (see Davis et al 1984).…”

“…ACTH was 1/500th as effective in the bioassay as a-MSH, while synthetic fl-endorphin (Beckman) exhibited no melanotropic activity at 100 ng ml-' and did not interfere with the normal z-MSH response at this dose (see also Davis et al 1984). None of the drugs tested had any direct effects on the bioassay at the experimental dilutions used.…”

“…For example, a dense network of GAD-positive, GABAergic fibres (Vincent, Hokfelt & Wu, 1982;Oertel, Mugnaini, Tappaz, Weise, Dahl, Schmechel & Kopin, 1982) and immunocytochemically stained serotonergic fibres (Westlund & Childs, 1982;Friedman, Krieger, Mezey, Leranth, Brownstein & Palkovits, 1983) as well as serotonergic S2 receptors (Davis et al 1984) have recently been discovered in the rat pars intermedia. However, only minimal effects of GABA (Tomiko, Taraskevich & Douglas, 1983;Stoll et al 1984) or serotonin (Vermes, Mulder, Smelik & Tilders, 1980;Randle, Moor & Kraicer, 1983a;Stoll et al 1984) application on POMC-derived peptide secretions have been demonstrated.…”

“…From all the POMC peptides to choose from, MSH was examined here as there is a simple, rapid bioassay available and its regulation appears to similarly reflect upon the others. (Davis, Lichtensteiger, Schlumpf & Bruinink, 1984). Explant preparation Details of the procedure for obtaining hypothalamo-hypophyseal explants are fully described elsewhere (Davis et al 1985).…”

Deregulated E2F Activity Induces Hyperplasia and Senescence-Like Features in the Mouse Pituitary Gland

“…One explanation could be that pRb, in addition to regulating E2F activity, also promotes differentiation and that increased E2F activity is unable to induce DNA replication in the differentiated gland. We excluded this possibility, showing that transient deregulation of E2F activity is sufficient to induce S phase regardless of the age of the mice and is therefore able to overcome the inhibition of a fully mature dopaminergic neural network (7,16,36). An alternative explanation, which is still to be tested, is that loss of pRb, unlike E2F deregulation, prevents the differentiation of certain cell types (e.g., stem cells) and that only this subpopulation of cells are capable of giving rise to tumors.…”