A PRIMING EFFECT OF LUTEINIZING HORMONE RELEASING FACTOR ON THE ANTERIOR PITUITARY GLAND IN THE FEMALE RAT

1974 ◽  
Vol 62 (3) ◽  
pp. 573-588 ◽  
Author(s):  
M. S. AIYER ◽  
SHARON A. CHIAPPA ◽  
G. FINK

SUMMARY The possibility that luteinizing hormone releasing factor (LH-RF) not only stimulates the secretion of luteinizing hormone (LH) but also has the ability to prime the anterior pituitary gland so that further exposure to LH-RF enhances the responsiveness of the gonadotrophs has been investigated. The effect of two successive i.v. injections of the same dose of LH-RF (50 ng/100 g body weight) on the concentration of LH in plasma was determined in rats anaesthetized with sodium pentobarbitone. Blood samples were collected from the external jugular vein immediately before and at frequent intervals after the injections of LH-RF, and plasma concentrations of LH and, in some samples, follicle-stimulating hormone (FSH) were measured by radioimmunoassay. In rats anaesthetized with sodium pentobarbitone at 13.30 h of pro-oestrus and injected i.v. with two successive doses of LH-RF, separated by an interval of 30, 60, 120 or 240 min, the LH response to the second injection was significantly greater than that to the first. The LH response was greatest when the two doses were separated by an interval of 60 min. The FSH response to the second injection of LH-RF given 60 min after the first was not significantly different from that to the first injection. Compared with pro-oestrus, the priming effect of LH-RF was much less at metoestrus and dioestrus, and could not be demonstrated at oestrus. Ovariectomy on the morning of dioestrus reduced the LH responses to the first and second injections of LH-RF given 60 min apart on the afternoon of pro-oestrus, an effect which was partially reversed by administration of oestradiol benzoate shortly after ovariectomy. These findings together with the fact that administration of oestradiol benzoate at metoestrus increased the magnitude of the priming effect of LH-RF at dioestrus suggest that the response at pro-oestrus is dependent upon the rise in plasma oestradiol-17β which reaches a peak on the morning of pro-oestrus. Although oestrogen plays an important role in determining the magnitude of the priming effect of LH-RF, it appears that none of the steroids secreted by either the ovaries or the adrenal glands mediates this effect since the profile and magnitude of the LH responses to the two doses of LH-RF injected at pro-oestrus into rats adrenalectomized and ovariectomized before the first injection of LH-RF were comparable to those in control animals. The possible role which the priming effect of LH-RF may play in the development of the preovulatory surge of LH in the rat and man is discussed.

1974 ◽  
Vol 62 (3) ◽  
pp. 553-572 ◽  
Author(s):  
M. S. AIYER ◽  
G. FINK

SUMMARY The role of ovarian hormones in the development of increased sensitivity of the anterior pituitary gland to synthetic luteinizing hormone releasing factor (LH-RF) which occurs before and during the preovulatory surge of luteinizing hormone (LH) in the rat has been examined. The response of the pituitary gland was determined, with respect to the secretion of LH and follicle-stimulating hormone (FSH), after the intravenous injection of 50 ng LH-RF/100 g body weight. The LH-RF was injected 30–60 min after the administration of sodium pentobarbitone at either 13.30 h or 18.80 h of pro-oestrus. Blood samples were collected immediately before and at frequent intervals after the injection of LH-RF, and the concentration of LH and FSH in these samples was measured by radioimmunoassay. Ovariectomy at 10.00–11.00 h of dioestrus reduced the LH response to LH-RF injected at 14.00 h of pro-oestrus, while oestradiol benzoate administered immediately after ovariectomy restored and even augmented this response. These data together with the finding that administration of the antioestrogen, ICI 46 474, at 17.00 h of dioestrus reduced the LH response to LH-RF injected on the afternoon of pro-oestrus indicates that the initial phase of increased pituitary sensitivity to LH-RF is dependent upon the marked rise in the concentration of oestradiol-17β in plasma which precedes the preovulatory surge of LH. The abrupt, marked increase in pituitary sensitivity to LH-RF, which, in the normal cycle, occurs between 14.00 and 18.30 h of pro-oestrus, failed to develop in rats ovariectomized on the morning of dioestrus whether or not oestradiol benzoate was administered after the operation. However, the LH response to LH-RF injected on the evening of pro-oestrus increased significantly when progesterone was administered at 13.00 h of pro-oestrus in rats ovariectomized and treated with oestradiol benzoate at 10.00–11.00 h of dioestrus. This suggests that the development of the second phase of increased pituitary sensitivity to LH-RF depends, at least partially, on progesterone acting on an oestrogen-primed pituitary gland. The concentrations of FSH in blood samples taken before injection of LH-RF at either 14.00 or 18.30 h of pro-oestrus were significantly greater in ovariectomized compared with those in sham-operated rats. In contrast the FSH responses, in terms of the mean maximal increments, were not significantly different in the various groups irrespective of the nature or time of operation or the time of injection of LH-RF. The FSH response to LH-RF was not appreciably altered by treatment with either oestradiol benzoate or progesterone immediately after ovariectomy although it was increased significantly by the sequential administration of oestrogen and progesterone. The significance of the findings that under certain conditions there were considerable differences between the LH and FSH responses to synthetic LH-RF is discussed with respect to the hypothesis that there is a common releasing factor for both gonadotrophins.


1977 ◽  
Vol 73 (3) ◽  
pp. 441-453 ◽  
Author(s):  
S. R. HENDERSON ◽  
CHRISTINE BAKER ◽  
G. FINK

SUMMARY Plasma concentrations of oestradiol-17β were measured by a non-chromatographic radioimmunoassay during the oestrous cycle, after the s.c. injection of 2·5 or 10 pg oestradiol benzoate (OB), or the s.c. implantation of Silastic capsules containing crystalline oestradiol-17β. The profile of endogenous plasma oestradiol-17β concentrations was similar to that reported by other workers, and lay between the concentrations produced by the low and high doses of OB. The rectangular pulses of increased plasma oestradiol concentrations, produced during the period of implantation of the Silastic capsules, were used to determine the time taken for oestradiol-17β to exert its facilitatory effect on the gonadotrophin response to LH-releasing factor (RF). In animals ovariectomized at dioestrus, oestradiol, at concentrations similar to those reached during the peak of the spontaneous surge, first reduced the LH response. However, after 7 h, responsiveness increased significantly to reach a peak at 12 h. The FSH response was also greatest 12 h after ovariectomy. In animals ovariectomized at metoestrus the effect of oestradiol on the LH response was significantly less than in rats ovariectomized at dioestrus, and the FSH responses were lower than those in animals bearing empty capsules and examined at the same time after ovariectomy. These findings together with the effects of long-term exposure to sodium pentobarbitone are considered with respect to the possible mechanisms, including the priming effect of LH-RF, which may produce increased pituitary responsiveness after ovariectomy and exposure to oestrogen.


1981 ◽  
Vol 91 (2) ◽  
pp. 347-351 ◽  
Author(s):  
R. MEIDAN ◽  
G. FINK ◽  
Y. KOCH

The ontogeny of the facilitatory effect of oestradiol and luteinizing hormone releasing hormone (LH-RH) on the responsiveness of the anterior pituitary gland to LH-RH has been studied in vitro using pituitary glands from female rats aged 15, 17, 20, 31, 35 and 38 days. The facilitatory effect of oestradiol was already well established by day 15, while the facilitatory effect of LH-RH (priming effect) developed only after day 17. Although it increased the overall response of the gland to LH-RH, oestradiol did not selectively enhance the priming effect of LH-RH. Both the effect of oestradiol and LH-RH reached a peak on day 25, 7 days before vaginal opening in this colony, and, as assessed by measuring pituitary LH contents, were not dependent upon the synthesis of LH. These data show that different mechanisms may be involved in the facilitation of pituitary responsiveness by oestradiol and LH-RH, but that both mechanisms appear to depend more upon an increase in the sensitivity of the receptor/release apparatus rather than in the gonadotrophin content of the gonadotrophs.


1981 ◽  
Vol 88 (2) ◽  
pp. 301-308 ◽  
Author(s):  
ALISON SPEIGHT ◽  
RACHEL POPKIN ◽  
A. G. WATTS ◽  
G. FINK

We have investigated the mechanism by which oestradiol-17β augments pituitary responsiveness to luteinizing hormone releasing factor (LH-RF). Adult rats were ovariectomized on the morning of dioestrus and implanted with either an empty silicone elastomer capsule or a capsule containing oestradiol-17β. Twelve hours later the LH response, tested by injecting 50 ng LH-RF/100 g i.v., was significantly greater in animals implanted with an oestradiol capsule compared with that in animals implanted with an empty capsule. The effect of oestradiol was blocked by sodium pentobarbitone administered 4 h before the test, and this block was overcome by infusing LH-RF during the 4 h period at doses which by themselves were not sufficient to evoke a large release of LH. We also measured LH-RF in pituitary stalk blood collected under Althesin anaesthesia between 4–6 and 12–13 h after ovariectomy and capsule implantation. The concentration of LH-RF in stalk plasma fell between these two collection periods in animals implanted with empty but not with oestradiol-filled capsules. The concentrations of LH-RF in stalk plasma, although relatively low, were significantly higher in animals bearing an oestradiol-containing capsule than the concentrations in peripheral plasma from similarly treated animals, and, by comparison with the LH-RF concentrations in peripheral plasma from animals infused with LH-RF, were sufficiently high to increase significantly the responsiveness of the pituitary gland. These data show that as well as acting directly on the pituitary gonadotrophs, oestradiol-17β increases the responsiveness of the anterior pituitary gland by a mechanism that involves the release and the priming effect of LH-RF.


2004 ◽  
Vol 287 (5) ◽  
pp. E818-E819 ◽  
Author(s):  
H. Maurice Goodman

This essay looks at the historical significance of an APS classic paper that is freely available online: Fevold HL, Hisaw FL, Leonard SL. The gonad stimulating and the luteinizing hormones of the anterior lobe of the hypophesis. Am J Physiol 97: 291—301, 1931 ( http://ajplegacy.physiology.org/cgi/reprint/97/2/291 ).


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