Sexual and Developmental Differences in Peptides Regulating Growth Hormone Secretion in the Rat

Abstract

Sex differences in the hypothalamic control of growth hormone (GH) secretion were investigated by measuring rat GH-releasing factor (rGRF) and somatostatin in male and female rats. Rat GRF-like immunoreactivity (rGRF-IR) was higher in the median eminence and hypothalamic tissue outside of the median eminence of adult (90-day-old) male compared to female rats. A similiar pattern of rGRF-IR content was found in the median eminence of 35-day-old rats. This sex difference developed between days 25 and 35 of age, during which time serum concentrations of insulin-like growth factor (IGF-1) and body weight increased in both sexes. To a lesser extent, the content of somatostatin-like immunoreactivity (SLI) was higher in the median eminence of adult female rats compared to male rats. Whole hypothalamic rGRF-IR and SLI contents were influenced only moderately by adult gonadectomy or gonadal steroid treatments. For example, estrogen increased rGRF-IR content in castrated rats, but orchidectomy alone or orchidectomy followed by testosterone did not influence rGRF-IR content. Additionally, whole hypothalamic SLI content was unaffected by orchidectomy or orchidectomy followed by testosterone or estrogen. One month after ovariectomy, rGRF-IR and SLI in whole hypothalamic fragments were similar to their respective contents in gonad-intact males. However, ovariectomy followed by estrogen or testosterone did not restore rGRF-IR content and partially restored SLI content to levels seen in gonad-intact females.

Sexually Dimorphic Effects of Aging on Rat Somatotropes and Lactotropes

“…This complies with the higher GH content and synthesis rate in male rats (for literature see Batson et al, 1989) and with the higher GH secretion of cultured male pituitary cells (Batson et al, 1989). Since GRF regulates the number of somatotrope mitoses (Billestrup et al, 1986), the higher hypothalamic GRF present in male rats (Gabriel et al, 1989) may account for the apparently higher number of GH-immunoreactive cells. ••Structure = contiguous immunocytochemically labeled areas of the image exceeding a particular density.…”

Sexual dimorphism of the somatotrophic axis

“…Androgen treatment in vivo has been reported to increase hypothalamic GRF protein and mRNA content in adult rats of both sexes (Zeitler et al 1990, Fernandez et al 1992, Hasegawa et al 1992, Chowen et al 1993. However, others have reported no change in hypothalamic GRF mRNA or GRF content after gonadectomy or testosterone treatment of adult male or female rats (De Gennaro Colonna et al 1991, Gabriel et al 1989, Maiter et al 1991b. The observation that hypophysectomy of adult rats blocks the increase in hypothalamic GRF mRNA after dihydrotestosterone treatment (Hasegawa et al 1992) suggests that any increase in GRF mRNA is a response to altered circulating patterns of GH, implying that androgens do not affect hypothalamic GRF synthesis directly.…”

“…Hypothalamic GRF content is greater in male than in female adult rats (Gabriel et al 1989, Maiter et al 1990, 1991a, Ono et al 1995 and hypothalamic GRF mRNA concentrations are two to three times greater in males than in females (Argente et al 1991, Maiter et al 1991b, Mizobuchi et al 1991, Hasegawa et al 1992, Chowen et al 1993. Similarly, in prepubertal lambs, the hypothalamic GRF content is approximately 50% greater in males than in females (Gatford et al 1997a).…”

“…The observation that hypophysectomy of adult rats blocks the increase in hypothalamic GRF mRNA after dihydrotestosterone treatment (Hasegawa et al 1992) suggests that any increase in GRF mRNA is a response to altered circulating patterns of GH, implying that androgens do not affect hypothalamic GRF synthesis directly. Most, but not all (Gabriel et al 1989), studies in rats suggest that oestrogen either suppresses (Fernandez et al 1992, Senaris et al 1992, Bennett et al 1996 or does not affect (Maiter et al 1991b) GRF synthesis and secretion. In addition to the direct effects of gonadal steroids at the hypothalamus, exposure to steroids during neonatal or prenatal life may have permanent effects on subsequent GRF production.…”

“…Consensus has not been reached regarding the effects of oestrogen on SRIF synthesis and secretion. In rats, in vivo oestrogen treatment increases hypothalamic content of SRIF protein and mRNA (Baldino et al 1988, Werner et al 1988, Gabriel et al 1989, Zorilla et al 1990, Senaris et al 1992, Bennett et al 1996 and addition of oestrogen to rat hypothalamic cell cultures inhibits SRIF secretion, but not synthesis (Fernandez et al 1992). In women, oestrogen treatment reduces the proportion who are refractory to stimulation of GH secretion by GRF, suggesting that SRIF secretion may be decreased by oestrogen (Devesa et al 1991).…”