Louise Ferland

Evidence for a role of endorphins in stress- and suckling-induced prolactin release in the rat

Injection of the opiate antagonist naloxone completely prevented the rise of serum prolactin induced by ether stress in intact male rats. Naloxone also led to a 50--95% inhibition of the marked elevation of plasma prolactin levels induced by suckling. These data suggest that endogenous opiates (endorphins) are involved in the stimulation of prolactin release induced by both stress and suckling in the rat.

Effect of Exposure to Cold on Hypothalamic TRH Activity and Plasma Levels of TSH and Prolactin in the Rat

No significant change in hypothalamic TRH content was found in rats during acute (5-240 min) exposure to cold (5 degrees C), in spite of rapid and sustained elevations in plasma TSH and thyroxine. Plasma PRL rose markedly in the first 15 min, but returned to normal thereafter. Chronic exposure to cold (32 days) was characterized by elevated plasma and pituitary levels of both TSH and PRL in the presence of an unaltered hypothalamic TRH content. If increased TRH release from the hypothalamus occurs during exposure to cold, as suggested by the pituitary-thyroid stimulation, either it is compensated for by an equal rise in synthesis, or the extra amount released is negligible in comparison with the hypothalamic content of TRH. The acute PRL response to exposure to cold may be related to an acute TRH release but could also result from the accompanying stress response acting by a mechanism independent of TRH.

Role of Sex Steroids on LH and FSH Secretion in the Rat

Elucidation of the structure of LH-RH (Matsuo et al., 1971; Burgus et al., 1971) has opened new possibilities for studies of the factors involved in the control of LH and FSH secretion. This presentation will attempt to summarize the data describing the role of estrogens and androgens as specific and important modulators of gonadotropin secretion. Using the rat as model, evidence vill be presented of a specific action of these steroids at the hypothalamic and pituitary levels.

Antidopaminergic activity of estrogens on prolactin release at the pituitary level in vivo.

Treatment of female or male rats with estradiol benzoate led to an almost complete reversal of the inhibitory effect of low doses of dopamine on prolactin secretion. These data indicate that estrogens which have previously been shown to exert a potent antidopaminergic activity on prolactin secretion in anterior pituitary cells in primary culture have similar effects in vivo.

High Inhibitory Activity of R 5020, A Pure Progestin, at the Hypothalamic-Adenohypophyseal Level on Gonadotropin Secretion

Synthetic progestins currently used in the contraceptive pill inhibited the luteinizing hormone (LH) responsiveness to LH-releasing hormone in cells in culture in a way undistinguishable from that of androgens. Moreover, they competed for binding of the 3H-labeled androgen R 1881 to the rat prostate androgen receptor and stimulated seminal vesicle and prostate weight in castrated rats. R 5020, a pure progestin, was without effect on the above-mentioned parameters. However, a complete inhibition of the LH surge measured in the afternoon of expected proestrus was obtained at a dose of R 5020 similar to that of D-norgestrel. The synthetic progestin was also found to inhibit ovulation and to delay vaginal cornification. The present data show that the synthetic progestins commonly used in the pill possess intrinsic androgenic activity which could well be responsible, to an unknown extent, for their effectiveness as contraceptive agents. R 5020, a synthetic progestin devoid of androgenic activity, is at least as potent as the most potent 19-nortestosterone derivative, D-norgestrel, in inhibiting gonadotropin secretion and other parameters of the estrous cycle in the rat. The availability of a pure progestin devoid of androgenic activity but highly effective as an inhibitor of gonadotropin secretion could be of great interest for the development of an improved contraceptive.

Site of the in vivo stimulatory effect of prostaglandins on LH release

A possible direct effect of prostaglandins E1 and E2 (PGE1 and PGE2) on luteinizing hormone (LH) release at the pituitary level was studied in vitro using anterior pituitary cells in primary culture, a system approximately 10-fold more sensitive to stimulation of LH release than previously used hemipituitaries. No effect of PGE1 or PGE2 could be detected on the time course of basal or LH-RH-stimulated LH release or on the LH responsiveness to LH-RH. This absence of a direct effect of PGEs at the pituitary level on LH release was confirmed by in vivo experiments using female rats under Surital anesthesia in the afternoon of proestrus. After intravenous injection, under these conditions, 15(S)-15-methyl PGE2 was 3-5 times more potent than PGE2 to increase plasma LH levels while PGE1 had about 50% the potency of PGE2. Injection of sheep anti-LH-RH serum one hour before PGE1 or PGE2 injection not only lowered basal plasma LH levels but prevented the rise induced by PGEs. These data indicate clearly that the increased plasma LH levels observed after in vivo PGE injection are secondary to a stimulation of LH-RH release while PGEs do not appear to have a significant effect on LH release at the pituitary level.

Androgen inhibition of basal and estrogen-stimulated prolactin binding in rat liver

Estradiol (E2 0.25 μg) administered twice a day for 7 days to rats ovariectomized 2 weeks previously caused a 4.5-fold increase in [125I]ovine prolactin (PRL) binding to a rat liver crude plasma membrane fraction. Testosterone (T, 500 μug) injected in combination with E2 caused a 75% reduction in PRL binding. In male rats (both intact and castrated) injected once daily with E2-benzoate (EB, 10 μg/100 g body wt), T-propionate (TP, 100 μg/100 g body wt.) caused a 62–73% decrease in E2-induced binding without affecting the high levels of plasma PRL induced by EB. DHT led to a significant inhibition of PRL binding at the relatively low doses of 10 and 2.5 μg/100 g body wt. in control and E2-treated ovariectomized rats, respectively. T was slightly less effective than DHT in reducing PRL binding. DHT was also found to be effective in reducing PRL binding to rat liver in rats hypophysectomized bearing a pituitary homotransplant, the level of binding decreasing from 10.7 ± 0.8% to 7.4 ± 0.7% (P < 0.01) in animals injected twice a day for 7 days (100 μug/100 g body wt.). A single injection of DHT caused a 24% reduction (P < 0.01) in PRL binding 12 h after its injection in E2-treated animals, the stimulatory effect of the estrogen being completely inhibited within 3–5 days of DHT treatment. These data indicate that androgens can effectively reduce prolactin binding to rat liver independently of their effect on plasma PRL.

Interactions of TRH, LH-RH, and Somatostatin in the Anterior Pituitary Gland

Publisher Summary This chapter focuses on the interactions of TRH, LH-RH, and somatostatin in the anterior pituitary gland. The secretory activity of anterior pituitary cells is controlled by specific hypothalamic hormones and the feedback action of gonadal, adrenal, and thyroid hormones. The neurohormones are released from the nerve endings containing these peptides in the median eminence and transported to their site of action by a small vascular portal system, growth hormone (GH) prolactin (PRL), adrenocorticotropin (ACTH), and thyrotropin (TSH) are secreted by different cell types, while there is evidence that luteinizing hormone (LH) and follicle-stimulating hormone (FSH) could originate from the same cell. The influence of the hypothalamus on LH, FSH, and ACTH secretion appears to be only positive, while the best available evidence indicates that both positive and negative effects are exerted on GH, TSH, and PRL secretion. The secretory activity of anterior pituitary cells is controlled by the specific hypothalamic hormones and the feedback action of gonadal, adrenal, and thyroid hormones. The neurohormones are released from the nerve endings containing these peptides in the median eminence and transported to their site of action by a small vascular portal system. The observed effects on the spontaneous proestrus plasma LH surge and ovulation support the possibility of developing a contraceptive method based on inhibitory L H-R H analogs.