Effects of Gonadal Steroids on Somatotroph Function in the Rat: Analysis by the Reverse Hemolytic Plaque Assay*

Abstract

The mechanism by which gonadal steroids modulate GH secretion is not known. We have used the reverse hemolytic plaque assay to examine whether gonadal steroid-induced modulation of GH secretion is effected by changes in the population of somatotrophs and/or alterations in their secretory properties. Two groups of Sprague-Dawley rats were studied: group 1 (n = 6) comprised male (M), castrate (Cx), and testosterone-replaced castrate male (Cx + T) rats and group 2 (n = 5) consisted of male (M), female (F), and 17 beta-estradiol-replaced castrate male (Cx + E) rats. The number of plaque-forming cells (expressed as both absolute number and a percentage of all cells) was determined, and secretory status was assessed by measuring plaque areas in response to 0, 0.01, 0.1, 1, 10, and 100 nM GHRH. While mean basal GH plaque areas were similar among the treatment groups of group 1, the maximal GH plaque area was significantly decreased in Cx [16.8 +/- 2.4 vs. 26.4 +/- 3.9 X 10(6) microns2 (mean +/- SEM); P less than 0.05], but not in Cx + T (27.5 +/- 4.1 microns2) rats. The GHRH EC50 was unaffected by castration or T replacement. The percentage and absolute population of somatotrophs were reduced in Cx, but not in Cx + T, rats, while the numbers of lactotrophs remained unchanged in these treatment groups. For group 2, the mean peak GH plaque area was reduced in Cx + E (16.5 +/- 2.9 microns2; P less than 0.001) compared to that in M rats (36.2 +/- 2.3 microns2), but was not significantly different from that in F (13.0 +/- 1.5 microns2) rats. The EC50 was significantly (P less than 0.025) greater in Cx + E (10.9 +/- 2.3 nM) and F (7.9 +/- 1.6 nM) compared to M rats (2.8 +/- 0.7 nM). The absolute somatotroph and lactotroph populations were increased in Cx + E compared to M and F rats, as were the populations of other pituitary cell types. Testosterone enhances GH secretion by increasing the secretory capacity, but not the sensitivity, of somatotrophs to GHRH and by recruiting the function of a subpopulation of somatotrophs. Estradiol reduces the secretory capacity and sensitivity of somatotrophs to GHRH, but increases the population of somatotrophs, lactotrophs, and non-GH- and non-PRL-secreting cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Differentiation of Mammosomatotrophs in Swine Adenohypophysis.

“…Using the thymidine kinase obliteration system, Borrelli et al [3] reported that both GH cells and PRL cells derive from a common GH-expressing stem GH cell, which terminally differentiates into GH and PRL cell populations in transgenic mice. These findings support a possible transformation of GH cells into PRL cells, with MS cells acting as an intermediate cell in swine adenohypophysis as previously described in the adenohypophysis of rats [5,13,26,35], humans [10] and bats [18].…”

Gender and gonadal influences on ghrelin mRNA levels in rat stomach

“…Nevertheless, it is possible that maturational changes in neuropeptide release or in the somatotroph responsiveness to somatostatin, growth hormone-releasing hormone (GHRH) and ghrelin might contribute to the pattern of circulating GH levels. Although data regarding gender differences in hypothalamic and somatostatin content are conflicting (17), it has been shown that in vitro GH responses to GHRH are influenced by age and gonadal status (18). Although no data are currently available regarding the influence of gonadal function on in vitro GH responses to ghrelin, it should be noted that GH responses to hexarelin are greater at the late postpubertal period (19).…”

Age-Related Changes in Growth Hormone and Prolactin Messenger RNA Levels in the Rat.

“…Estrogen stimulates the proliferation of pituitary cells including PRL cells (Takahashi et al, 1984). Ho et al(1988) recently found by reverse hemolytic plaque assay that estrogen increased the number of GH cells, PRL cells, non-GH-and non-PRL-secreting cells. We had previously reported that long-term ovariectomy prevented the age-related increase in the number of PRL cells (Takahashi and Kawashima, 1983).…”