Intrapituitary Regulatory System of Proliferation of Mammotrophs in the Pituitary Gland

Anterior pituitary cells produce growth factors plus cytokines and their receptors. Although some of these pituitary growth factors and cytokines are known to be involved in the control of cell differentiation, proliferation and hormone production in the pituitary gland, their physiological roles remain unknown. Lots of evidence indicates that they are involved in the regulation of prolactin-secreting mammotroph cell proliferation. The regulation of mammotroph functions is a suitable system for understanding the intrapituitary regulatory system operated by growth factors and cytokines, since mammotrophs are the most actively proliferating cells in female pituitary glands. This review discusses the possible intrapituitary regulation of mammotroph differentiation and proliferation in rat and mouse pituitaries

Transcription factor Runx3 in the mouse hypothalamo-pituitary-gonadal system

Runx3 is a transcription factor that belongs to the Runx family. Female Runx3 knockout (Runx3−⁄−) mouse was anovulatory and infertile. Ovarian transplantation experiment suggested that lack of ovulation in Runx3−⁄− mice was caused by alteration of gonadotropin secretion in Runx3−⁄− mice. Cyp11a1 mRNA expression was less in Runx3−⁄− mouse ovaries than in wt ones. Hypothalamic Gnrh1 mRNA was increased, and Kiss1 mRNA expression in the anteroventral periventricular nucleus was decreased, but Kisspeptin mRNA in the arcuate nucleus was increased in Runx3-/- mice. Pituitary Fshb mRNA levels were increased in Runx3−⁄− mice. Cholesterol side-chain cleavage enzyme gene (Cyp11a1) expression was decreased in ovaries of Runx3−⁄− mice. These findings suggest that anovulation in Runx3−⁄− mice was partly due to the alterations in hypothalamus-pituitary-ovary system. Runx3 plays a key role in female reproduction through alteration of gonadotropin secretion

Induction of mammotroph development by a combination of epidermal growth factor, insulin, and estradiol-17β in rat pituitary tumor GH3 cells

Several reports have indicated that prolactin-secreting cells (PRL cells) are generated from growth hormone-secreting cells (GH cells). We have shown that treatment with a combination of epidermal growth factor (EGF), insulin, and estradiol-17beta (E-2) induces the appearance of PRL cells in pituitary tumor GH3 cells. The aim of the present study was to clarify the involvement of mitosis in the cytogenesis of PRL cells in rat pituitary and GH3 cells. The effects of the treatment with EGF, insulin and E-2 on DNA-replication were studied by detecting the uptake of bromodeoxyuridine (BrdU) into the nucleus. In cultured rat pituitary cells, BrdU-labeled PRL cells were observed irrespective of the hormone treatment. In GH3 cells, BrdU-Iabeled GH cells and mammosomatotrophs (MS cells) were detected; BrdU-labeled PRL cells were not detected, however, when GH3 cells were treated with BrdU for 3 hr and then immediately examined for BrdU-labeling. BrdU-Iabeled PRL cells were found only when GH3 cells treated with BrdU were allowed to grow for another 3 days. This finding suggests that during the additional 3-day culture, BrdU-labeled PRL cells were generated from BrdU-Iabeled cells other than PRL cells. These results indicate that PRL cells are transdifferentiated from GH cells or VIS cells in GH3 cells by a combined treatment with EGF, insulin and E-2, while PRL cells in rat pituitaries are able to proliferate in response to the hormone treatment. Thus, there may be two pathways for cytogenesis of PRL cells the transdifferentiation of GH cells or VIS cells, and a self-duplication of PRL cells

Gene Expression and the Physiological Role of Transforming Growth Factor-α in the Mouse Pituitary

Transforming growth factor-alpha (TGF-alpha), a member of the epidermal growth factor (EGF) family, is produced within the mouse anterior pituitaries. However, the cell types of TGF-alpha-expressing cells and the physiological roles of TGF-a within mouse pituitary glands remain unclear. The aim of the present study was to localize TGF-alpha mRNA-expressing cells, and to clarify the involvement of TGF-alpha in estrogen-induced DNA replication in mouse anterior pituitary cells. Northern blot analysis demonstrated TGF-alpha mRNA expression in adult male and female mouse anterior pituitaries. In situ hybridization analysis of the pituitaries in these mice showed that TGF-alpha mRNA-expressing cells in the anterior pituitary are round, oval, and medium-sized. TGF-alpha mRNA was colocalized in most of the growth hormone (GH) mRNA-expressing cells, while only some of the prolactin (PRL) mRNA-expressing cells. DNA replication in the anterior pituitary cells was detected by monitoring the cellular uptake of a thymidine analogue, bromodeoxyuridine (BrdU) in a primary serum-free culture system. Estradiol-17beta (E2) and TGF-alpha treatment increased the number of BrdU-labelled mammotrophs, indicating that E2 and TGF-alpha treatment stimulates the DNA replication in mammotrophs. Immunoneutralization of TGF-alpha with anti-TGF-alpha-antibodies nullified the E2-induced increase in DNA replication. RT-PCR analysis of TGF-alpha mRNA expression in ovariectomized female mice revealed that E2 increases TGF-alpha mRNA levels. These results indicate that the TGF-alpha produced primarily in the somatotrophs mediates the stimulatory effects of estrogen on the DNA replication of pituitary cells in a paracrine or autocrine manner

Paternal Care Behaviors of Japanese Giant Salamander Andrias japonicus in Natural Populations

Abstract Parental care among salamanders is typically provided by females. A rare case of parental care by male salamanders appears to occur in Cryptobranchidae. Yet, paternal behaviors have rarely been reported from natural populations of any Cryptobranchid salamanders, and their adaptive significance is poorly understood. The present study aimed to examine paternal care behaviors in a fully aquatic Japanese giant salamander (Andrias japonicus) in situ. At the beginning of the summer breeding season, large males, called den-masters, occupy burrows along stream banks for breeding and nesting. We videotaped post-breeding behaviors of two den-masters that stayed with the eggs, one in a natural and the other in an artificial nest in natural streams. We identified three behaviors, tail fanning, agitating and egg eating, to be parental care. Tail fanning provides oxygenated water for the eggs. We found that the den-master in the artificial nest, where dissolved oxygen level was lower, displayed tail fanning more frequently. Agitating the eggs with its head and body likely prevents yolk adhesions. The den-masters selectively ate whiter eggs that appeared to be dead or infected with water mold. This behavior, which we termed hygienic filial cannibalism, likely prevents water mold from spreading over healthy eggs. Digital video images relating to this article are available at http://www.momo-p.com/showdetail-e.php?movieid=momo140906aj01a, http://www.momo-p.com/showdetail-e.php?movieid=momo140906aj02a, http://www.momo-p.com/showdetail-e.php?movieid=momo140906aj03a and http://www.momo-p.com/showdetail-e.php?movieid=momo140906aj04a.</jats:p

Physiological roles of Runx3 in female reproductive organs in mice

Runx3(Runtdomaintranscriptionfactor3)はRunxファミリーに属する転写因子で雌マウスにおいてRunx3 mRNAは, 卵巣や子宮に発現していた。雌のRunx3(-/-)マウスは不妊であった。Runx3(-/-)マウスは卵胞形成異常を起こしており, 無排卵であった。一方で, 排卵能および黄体形成能は有していた。以上より, Runx3は卵胞形成および排卵制御に関与していることを明らかにした。Runx3(-/-)マウスの子宮は萎縮している。子宮内膜上皮細胞では, E2依存性の細胞増殖が起こらなかった。しかし,子宮内膜間質細胞では, E2, P4存在下で正常に細胞増殖が起きた。以上より, Runx3はE2による子宮の細胞増殖に関与していることを明らかにした