Facilitation of Luteinizing Hormone Release by Progesterone in Proestrous Rats

Abstract

SynopsisIn order to elucidate the facilitation of ovulatory release of luteinizing hormone (LH) and subsequent ovulation, subcutaneous injection or intrahypothalamic implantation of progesterone was carried out on the morning of proestrus in 4-day cyclic rats . By injecting progesterone on the morning or early afternoon of proestrus , an approximate 3 hr advancement of ovulatory release of LH was demonstrated by confirming the occurrence of ovulation on the next morning after timed hypophysectomy performed on the afternoon of proestrus. Ovulation also occurred about 3 hr earlier in the estrous morning when progesterone had been given on the morning of proestrus. The minimum effective dose of progesterone to facilitate LH-release was somewhere between 0 .1 and 0.625mg per rat. Facilitation of LH-release by steroid administration on the morning of proestrus is not entirely specific for progesterone. Norethisterone, medroxyprogesterone acetate , and desoxycorticosterone(DOC) also induced the advanced release of LH. Facilitation of ovulatory release of LH was induced also in the rats having progesterone crystals implanted in the median eminence-arcuate region of the hypothalamus on the morning of proestrus. These results indicate that a neural timing factor regulating the onset of LHrelease in proestrus is labile to a certain extent, and that it operates about 3 hr in advance when it is exposed to progesterone given on the morning of proestrus , and that the appearance of facilitatory action of progesterone depends on the pre-existing estrogen level in the circulating blood.It is well known that progesterone has a biphasic effect on ovulation and, according to the conditions, it can either stimulate or inhibit the release of luteinizing hormone (LH) (for a review see Everett, 1964; Sawyer, 1964;Rothchild, 1965;Davidson, 1969). A lack of spontaneous ovulation during pregnancy or pseudopregnancy is evidence of the inhibitory effect on LH-release of endogenous progesterone, the secretion of which is increased during gestation. Exogenous progesterone also inhibits or delays spontaneous ovulation in rats and in many other species. The stimulating effect of progesterone on ovulation has been shown under several conditions, e. g. in persistent estrous rats (Everett, 1940), in normal 5-day cyclic rats (Everett, 1948; BrownGrant, 1967) and in immature rats primed with pregnant mare's serum gonadotropin Meyer, 1963 and1965).With regard to the ovulation induction in adult rats, it was previously suggested by Everett(1948) that the appearance of stimulating action of progesterone depends on the pre-existing estrogen level in the circulating blood. In our previous work, progesterone administered into 4-day cyclic rats induced a delayed ovulation only when injected before 2 a. m. proestrus, by which time estrogen secretion had not attained the maximum (Hori et al., 1968), and it accounted for uterine distension and uterine weight increase on the day of proestrus though it was not enough for the release of LH on the same day (Kob...

Facilitation by Progesterone of Ovulating Hormone Release in Sodium Pentobarbital-Blocked Proestrous Rats

“…On the contrary, when PB is administered at 16: 00 proestrus, recovery of CNS from the drug suppression occurs earlier and many rats spontaneously release OH thereafter. In addition to the previous reports (Zeilmaker, 1966;Redmond, 1968;Uchida et al, 1969b andKobayashi et al, 1970), the fact that the injection of progesterone is able to produce OH release even after the CNS was suppressed by small doses of PB in proestrous rats also indicates the facilitatory action of this steroid. Greenwald (1971) demonstrated a similar action of progesterone to induce ovulation in phenobarbital-blocked proestrous hamsters.…”

“…On the other hand, it is considered that the rats given smaller doses of PB, 25 or 22.5mg/kg, at 17: 00 proestrus still have the neural activity for a while, which, however, is too weak and insufficient to induce OH release by itself, and that such a weak and insufficient neural stimulus may be effectively accepted by the medial basal hypothalamus to induce OH release from the anterior pituitary when progesterone is administered. In fact, implantation of progesterone crystals into the medial basal hypothalamus on the morning of proestrus facilitates OH release, suggesting that the facilitatory mechanism of progesterone is the increase in the sensitivity of this hypothalamic area to the neural stimulus coming from the higher CNS (Kobayashi et al, 1970).…”

“…The stimulatory effect of progesterone has been demonstrated under various conditions, e.g., in persistent estrous rats (Everett, 1940), in normal 5-day cyclic rats (Everett, 1948;Brown-Grant, 1967) and in immature rats primed with pregnant mare's serum gonadotropin Meyer, 1963 and1965). In addition, the condition for a facilitatory action of progesterone exists on the day of proestrus in normal cyclic rats and the release of OH can be advanced by a few hr by the injection of exogenous progesterone (Zeilmaker, 1966;Redmond, 1968).In the previous studies, we also elucidated the facilitation of OH release in 4-day cyclic rats either by injecting progesterone subcutaneously or by implanting the steroid into the median eminence-arcuate region of the hypothalamus on the morning or early afternoon of proestrus (Kobayashi et al, 1970). It was further presumed in the rats given acute hypothalamic deafferentation with a small knife that the facilitation by progesterone of OH release may be due to the increase in the responsiveness of the medial basal hypothalamus to the ovulatory stimulus coming from the higher CNS (Kobayashi and Miyake, 1971).…”

“…In the previous studies, we also elucidated the facilitation of OH release in 4-day cyclic rats either by injecting progesterone subcutaneously or by implanting the steroid into the median eminence-arcuate region of the hypothalamus on the morning or early afternoon of proestrus (Kobayashi et al, 1970). It was further presumed in the rats given acute hypothalamic deafferentation with a small knife that the facilitation by progesterone of OH release may be due to the increase in the responsiveness of the medial basal hypothalamus to the ovulatory stimulus coming from the higher CNS (Kobayashi and Miyake, 1971).…”

Localization and Mechanism of Stimulatory Feedback Action of Estrogen: Effect of Limbic Forebrain Implantation of Estradiol Benzoate on Advancement of Ovulation

“…Presumably, the inhibition of LH release by systemic injection may be a representation of action of some negative feedback areas of estrogen in the hypothalamus as well as in the extrahypothalamus (Lisk, 1960;Davidson, 1969 such as the medial AMYG or the BST, which is sensitive to EB, and giving 24-hour rhythmicity (Kawakami and Kimura, 1974b). Such nature of the MPO, lack of functional sensitivity to ovarian hormones, is also supported by the experiments of Kobayashi et al (1970) and Weick and Davidson (1970), in which progesterone implantation into the MPO did not induce facilitation of ovulatory hormone release. From the prevention by the AHD of EB implantation effect in the ARC on induction of ovulation, it is supported that this area requires the neural influence presumably coming from the medial AMYG and the BST via the MPO …”