Cellular proliferation in the anterior pituitary gland of normal adult rats: Influences of sex, estrous cycle, and circadian change

Abstract

Proliferative activity of the anterior pituitary gland in 10 week-old male and female rats under normal conditions was investigated by counting mitotic figures and using single and double immunostaining of 5-bromo-2'-deoxyuridine (BrdU), proliferating cell nuclear antigen (PCNA), and six pituitary hormones. To determine which proliferative changes depend on the estrous cycle and circadian changes, respectively, six groups of female and two groups of male rats were studied at various times of day. Additionally, BrdU-incorporated cells were further classified by the six types of hormones they contained, or as immunonegative cells. Cell proliferative activity in the females fluctuated drastically with the highest activity in estrus and the lowest in diestrus. In the males, proliferative activity was at a relatively low level, and was similar to that in females in proestrus or early estrus, with the greater activity at night. Identified by their pituitary hormones, the distribution of the proliferating cells was almost the same in each sex, with prolactin (PRL) cells accounting for the highest proportion, followed by growth hormone (GH) cells, and adrenocorticotropic hormone (ACTH), luteinizing hormone (LH), follicle stimulating hormone (FSH), and thyroid stimulating hormone (TSH) cells. These percentages agreed well with previously reported levels of cell types among all pituitary cells of the rat. It is therefore suggested that the life span and cycle of rat pituitary cells does not differ among cell types. In another test, male and female rats were given BrdU continuously via an osmotic pump for 8 days to compare cell proliferative activity between sexes, exclusive of the influence of estrous cycle and circadian changes. In this way, we were able to demonstrate that the cumulative incorporation of BrdU in females was consistently twice as high as in males over a constant period of time, and to conclude that cell renewal occurs at a doubled rate in the pituitary of female rat.

The number of lactotrophs is reduced in the anterior pituitary of streptozotocin-induced diabetic rats

“…A decrease in both production and secretion could result in no change in static GH protein content. Somatotroph turnover could be less responsive in this paradigm as lactotrophs are more sensitive to changes in the hormonal environment than other pituitary cell types [4].…”

“…However, a decrease in the number of lactotrophs could also explain a reduction in PRL output, with no loss in synthetic capacity of individual lactotrophs. The anterior pituitary undergoes cellular turnover during adulthood and this is affected by changes in the hormonal environment [4]. Hence, the cellular makeup of the anterior pituitary could be affected in diabetes mellitus.…”

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

“…It is well known that PRL cells have the ability to replicate DNA and to divide in rat and mouse pituitary glands in vivo and in vitro in response to estrogen and various growth factors (Takahashi et al ., 1984;Oishi et al ., 1993;Oomizu et al ., 2000). In contrast, it is evident from the present study that PRL cells of GH3 cells are unable to replicate DNA molecules.…”

“…In contrast, the proliferation of PRL cells is a well-known event in the rat and mouse pituitary gland (Takahashi, 1995). The highest mitotic activity of PRL cells is observed at estrus in the female rat pituitary (Takahashi et al ., 1984;Oishi et al ., 1993). As estrogen treatment stimulates the proliferation of PRL cells (Lloyd et al ., 1975;Takahashi and Kawashima, 1987;Oomizu et al ., 2000), the high proliferating activity of PRL cells is caused by the increase in estrogen secretion during the proestrous and estrous days.…”

Biological rhythms and fertility: the hypothalamus–pituitary–ovary axis

“…48 It is of note that gonadotropic cell proliferation in the pituitary follows a diurnal rhythm and is synchronized with the estrous cycle in normal adult rats. 49 Recently, using a human autopsy dataset, Wunderer et al examined the postmortem pituitaries of 52 individuals deceased for different causes at various times of the day (dusk, night, dawn, or day). 50 Clock gene expression (Per1, Cry1, Clock, and Bmal1) was found in the pituitary tissue; however, while the expression of mRNA of Cry, Clock, and Bmal1 did not vary in relation to the time of the death, Per1 mRNA expression was significantly higher in case of death occurring during the day than at dusk, irrespective of postmortem interval, age, or sex.…”