Effects of in vivo gonadal hormone environment on in vitro hGRF-40-stimulated GH release

His-dTrp-Ala-Trp-dPhe, Lys-NH2 (GHRP-6) is a synthetic compound that releases GH in a dose-response and specific manner in several species and that may well be related to an endogenous compound of similar structure. The aim of this study was to investigate the in vivo GH responses to GHRP-6 in pentobarbital anesthetized rats. Specifically and in order to avoid the influence of endogenous GHRH and somatostatin secretion we studied the GH responses to GHRP-6 in animals with surgical ablation of the hypothalamus, confirmed by histological assessment, as well as in hypophysectomyzed-transplanted rats bearing two hypophyses under the renal capsule. Since it has been previously reported that rats pretreated with GHRH (10 µg/kg i.p. every 12 h for 15 days) rather than saline-treated rats have greater GH responses to acutely administered GHRH, we compared the self-potentiating effect of chronic GH pretreatment with GHRP-6 (10 µg/kg i.p. every 12 h). Furthermore we also studied the influence of estrogens, glucocorticoids, free fatty acids (FFA) and bombesin on somatotroph responsiveness to GHRP-6 in intact rats. We found a greater GH response to GHRP-6 in rats that underwent a surgical ablation of the hypothalamus 36 h prior to the test than in sham-operated rats. A direct stimulatory effect of GHRP-6 on in vivo GH secretion was demonstrated by a clear GH response to GHRP-6 in hypophysectomyzed-transplanted rats. In addition, we found a similar response whether the animals were pretreated with GHRH or GHRP-6 over the previous 2 weeks. Finally, we found that both estrogen- and testosterone-treated rats have greater GH responses to GHRP-6 than untreated rats. On the other hand, chronic dexa-methasone administration, acute elevation of circulating FFA levels and bombesin administration markedly inhibited GH responses to GHRP-6. In contrast to the effects exerted on GH responses to GHRP-6 estrogen administration led to a decrease in GH responses to GHRH while dexamethasone did not affect the GH responses to GHRH, highlighting a differential regulation of these hormones on somatotroph responsiveness to these peptides.

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Regulation of His-dTrp-Ala-Trp-dPhe-Lys-NH2 (GHRP-6)-lnduced GH Secretion in the Rat

Mallo

Álvarez²,

Benítez³

et al. 1993

“…GH secretion is controlled by GHRH and somatostatin [ 1] and peripheral signals such as gonadal hormones [2,3], In adult rats, in vivo pituitary responsiveness to GHRH was shown to de crease after orchidectomy [2,3] and increased after testos terone administration [2, 4], Therefore, testicular factors other than testosterone may be involved in the modula tion of pituitary responsiveness to GHRH. This is because the in vitro GH response to GHRH remained unaltered after preincubation of dispersed cells with testosterone [2] and the increased serum testosterone levels in orchidec tomized males after testosterone administration were not accompanied by a full recovery of the in vitro pituitary response to GHRH [5]. In the present work we demon strate that GHRH-induced GH secretion decreased in or chidectomized males, and remained normal after sup pression of testosterone secretion by ethylene dimethane sulphonate (EDS).…”

mentioning

confidence: 50%

Growth Hormone-Releasing Hormone-Induced Growth Hormone Secretion in Adult Rats Orchidectomized or Injected with Ethylene Dimethane Sulphonate

Aguilar

Pinilla²,

Tena‐Sempere³

1993

It is well known that GHRH-induced GH secretion decreases after orchidectomy. To verify if testicular factors other than testosterone are involved in this effect, the GHRH-induced GH secretion and testosterone plasma levels were compared in adult male rats that were either intact, treated with ethylene dimethane sulphonate (EDS) (a specific toxin for Leydig cells), orchidectomized or testosterone-treated orchidectomized. We found that testosterone plasma levels and ventral prostate weight decreased to a similar extent in orchidectomized and EDS-treated males. GHRH-induced GH secretion only decreased in orchidectomized males. We conclude that testicular factors, other than androgens, increase GHRH-induced GH secretion.

“…In vivo treatment with testosterone enhances, while in vivo treatment with estrogen diminishes in vitro GRF-stimulated GH release [33,34]. The effects of in vitro estrogen treatment on GH release and synthesis in culture are conflicting [30,[35][36][37].…”

Section: Discussionmentioning

confidence: 99%

Influence of in vivo Reproductive Endocrine State on Growth Hormone-Releasing Factor Stimulated Adenylate Cyclase Activity in Anterior Pituitary Fragments

Gabriel

Hunnicut²,

Millard³

et al. 1993

The growth hormone releasing factor (GRF) stimulated adenylate cyclase activity was evaluated in membrane fractions of anterior pituitary glands from male and female rats and in gonadectomized rats following in vivo gonadal steroid treatments. The baseline adenylate cyclase activity was lower in random estrous cycle female rats as compared with males. When estrous cycle phases were evaluated, diestrus 1 females had a lower basal activity as compared with males, while proestrus females were similar to males. The maximal stimulation of adenylate cyclase activity by GRF (i.e. V_max) was lower in random estrous cycle female rats than in males. This lower V_max, relative to males, was more pronounced in diestrus 1 than in proestrus females. There was little difference in the ED₅₀ for GRF-stimulated adenylate cyclase activity among these groups. The adenylate cyclase activity was altered 1 week after gonadectomy or 1 week after gonadectomy plus simultaneous in vivo gonadal steroid treatment. The expression of data as a function of whole tissue (content) or as a function of protein (concentration) influenced magnitude and direction of these treatment effects. This may reflect the proliferation of nonsomatotroph cell populations and altered protein synthetic activity following reproductive endocrine manipulations. When expressed as a whole tissue content, the baseline adenylate cyclase activity was unchanged after gonadectomy when compared to same-sex, gonadal-intact cohorts. However, an increase in the V_max for GRF-stimulated adenylate cyclase activity was found in gonadectomized rats relative to sham-operated, gonadal-intact cohorts. When the same data were calculated relative to protein concentration, a decrease in baseline was found following orchidectomy, but not following ovariectomy, when compared to sham-operated, gonadal-intact cohorts. The corresponding V_maχ for these groups, expressed as a concentration, decreased after orchidectomy, but increased after ovariectomy. Gonadectomy plus estrogen treatment decreased both baseline and V_max for GRF-stimulated adenylate cyclase activity. This potent decrease was evident when compared to either same-sex, gonadectomized, or gonadal-intact cohorts for both forms of data expression. Basal and maximally stimulated adenylate cyclase activities following ovariectomy plus testosterone treatment were similar to gonadal-intact females when the data were expressed as a content, but similar to ovariectomized rats when the same data were expressed as a concentration. None of the above treatments significantly altered the ED₅₀ for GRF-stimulated adenylate cyclase activity. These data indicate sex differences for in vitro basal and GRF-stimulated adenylate cyclase activity in rat anterior pituitary membranes. With heterotypic in vivo steroid treatment, estrogen was inhibitory, while testosterone partially was stimulatory to basal and GRF-stimulated adenylate cyclase activity.