An immunohistochemical study on the cytogenesis of adenohypophysial cells in fetal rats.

I. Introduction CASCADES of interacting regulatory genes controlling developmental pathways have been defined in organisms such as Drosophila (1–9) and the nematode Caenorhabditis elegans (10–12). The developmental regulators include transcription factors, kinases, phosphatases, growth factors,receptors, and cell-adhesion molecules. In Drosophila, products of maternally expressed genes control expression of zygotic segmentation genes, the products of which regulate homeotic gene expression; regulation is also exerted between genes of the same class. As a result, the embryo is divided into a meshwork of metameric units, each expressing a unique combination of homeotic genes. These genes contain a conserved homeobox, encoding a 60-amino acid homeodomain which functions in DNA binding. By acting as transcription factors, the homeodomain proteins orchestrate activation of a unique combination of target genes which makes the cells enter a specific morphogenetic pathway. The molecular mechanisms underlying regu...

Transcriptional Control of GH Expression and Anterior Pituitary Development

Reverse hemolytic plaque assays and immunocytochemistry were used to monitor the ontogeny of individual hormone-secreting and hormone-containing cells in rats. Monodispersed anterior pituitary cells from fetal rats (sex unspecified) and neonatal rats of each sex were cultured for 24 h and then subjected to immunocytochemistry or plaque assays for PRL or GH. PRL secretors first appeared in appreciable numbers in cultures from 4-day-old animals, and by day 5, they accounted for 8–12% of all cells in culture. The percentage of GH secretors rose to a peak on day 5 (comprising ∼40% of all cells), when the values were slightly higher than those observed previously in adults. The percentage of cultured cells from 4- to 5-day-olds that released PRL or GH was not influenced by the sex of the donor animal and was consistent with immunocytochemical estimates. Using a sequential plaque assay that enabled the detection of both GH and PRL release from the same cells, we found that of every 100 pituitary cells from 5-da...

Ontogeny of Prolactin Cells in Neonatal Rats: Initial Prolactin Secretors also Release Growth Hormone*

Immunoreactive luteinizing hormone-releasing hormone (LHRH) was first detected at 15 days of gestation in ganglion cells associated with the peripheral, intracranial, and central parts of the nervus terminalis of the rat. LHRH was not detected in any other structure of the central nervous system at this age.



In the 17-day-old fetal rat, 62% of the total LHRH-reactive neuronal population was found in ganglion cells of the nervus terminalis. At this same age, immunoreactive beta-luteinizing hormone (β-LH) was first seen in gonadotropes of the anterior pituitary gland.



At 19 days of gestation, 31% of the total number of LHRH-reactive neurons observed in the rat brain was found in the nervus terminalis, and immunoreactive processes were first seen in the organum vasculosum of the lamina terminalis and in the median eminence.



Our data indicate that from 15 to 19 days of gestation the nervus terminalis is a principal source of LHRH in the fetal rat. Presence of the decapeptide in the nervus terminalis prior to appearance of β-LH in the anterior pituitary suggests a possible role for LHRH in this system on maturation of the gonadotropes and differentiation of the brain-pituitary-gonadal axis.

Ontogenesis of neurons producing luteinizing hormone-releasing hormone (LHRH) in the nervus terminalis of the rat.

Studies on the proliferation and differentiation of the cells in the rat anterior pituitary were reviewed. The mitotic rate of anterior pituitary is low in the control adult animal, but it increased by stimulation, such as by ablation of the target organ. A high mitotic rate was also reported during ontogenesis of the pituitary. Concomitant with this augmented mitosis, the number of those cells that are double-labeled with the marker of proliferation and the antibody to pituitary hormones increased as well. The percentage of these double-labeled cells in all the proliferating cells is less than 10%, suggesting that about 1/10 of the proliferating cells are involved in producing pituitary cells. This percentage for GH cells is 30-40% at most, suggesting very active production of them. The percentage of the double-labeled cell in all the hormone-producing cells is within 10% in all cell-types of the pituitary, including GH cells. When the proliferation is detected by a more sensitive method, this percentage increased to 20-40%, suggesting that the self-mitosis of the pituitary cells contributes considerably to their proliferation at a certain period during their ontogenesis.

Proliferation and differentiation of rat anterior pituitary cells.

The onset of hormone synthesis in the rat fetal pituitary gland was studied with the use of the peroxidase labelled antibody method. On the 16th day of fetal life, cells containing immunoreactive ACTH appeared in the primordial cell outgrowth of the Rathke's pouch. In some fetuses, also prolactin cells could be detected at the same developmental stage and these cells were present consistently on subsequent days. Differentiation of ACTH and prolactin cells was followed by onset of TSH, LH and GH synthesis on the 17th, 18th and 19th day of gestation, respectively.

Functional differentiation of the fetal anterior pituitary cells in the rat.

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Functional differentiation of the fetal anterior pituitary cells in the rat.