LH Release In Rats Research Articles

A dopamine agonist stimulates progesterone secretion from adrenal gland

Administration of either progesterone (P) or a dopamine agonist, Legrotrile mesylate (LM), have been shown to induce the ovulatory release of LH in rats. In order to elucidate the mode of action of dopamine agonists we studied the effects of LM on P secretion by the adrenals. A subcutaneous injection of LM, in doses which induce ovulation, stimulated adrenal P secretion in ovariectomized, estrogen-primed rats and in castrate male rats. Peak plasma P concentrations were found at 2 h with a gradual return to pre-injection levels at 6 hrs following LM injection. These results raise the possibility that P increments following LM administration may be responsible for inducing ovulation in young and old rats. There is considerable evidence to show that modification of hypothalamic monoamine metabolism by pharmacologic agents results in markedly altered pituitary gonadotropin secretion [1]. Lergotrile mesylate (LM), a dopamine agonist, has been shown to advance the ovulatory release of LH on proestrus and induce ovulation and cyclicity in anovulatory aged rats [2,3]. Everett [4] observed that progesterone (P) administration induced ovulation in rats rendered anovulatory under constant light and also advanced ovulation by one day if administered to 5-day cycling rats. A similar effect of LM on ovulation advancement has been noted (Clemens, personal communication). These similarities in action of P and LM on ovulation in young and aged rats, led us to speculate that LM may stimulate P secretion which in turn may elicit the discharge of ovulatory hormones. To test this hypothesis we examined the effects of LM on progesterone secretion in gonadectomized rats.

Effects of chemical lesion of the ventral noradrenergic bundle or the medial preoptic area on preovulatory LH release in rats.

The noradrenergic innervation of the medial preoptic area (MPO) and the hypothalamus is provided by mesencephalic neurons via the ventral noradrenergic tract. Fibers of these neurons emerge through the MPO. Bilateral microinjections of 6-OHDA into the ventral noradrenergic bundle (VNB) depletes large parts of the diencephalon of norepinephrine (NE) and dopamine (DA). Since the total hypothalamic DA content is of intrahypothalamic origin, 6-OHDA injection into the VNB does not reduce hypothalamic DA content. Similarly microinjections of 6-OHDA into the MPO reduces hypothalamic and preoptic NE content without altering NE concentrations in other diencephalic structures. Microinjections of 6-OHDA and of the carrier solution of 6-OHDA into the VNB or into the MPO of female rats with regular estrous cycles results in a slight disturbance of the cyclic activity for few days. Within 1--4 days normal cyclic activity is resumed. Preovulatory LH release is substantially reduced 8--12 days after injection of 6-OHDA into the VNB or into the MPO. On the basis of these and previous results it is concluded that the availability of NE in the MPO is an important factor in determining the hight of the preovulatory LH surge.

Interactions of the Light-Dark Cycle, Adrenal Glands and Time of Steroid Administration in Determining the Temporal Sequence of LH and Prolactin Release in Female Rats

The purpose of this study was to determine the effects of the light-dark cycle, adrenal glands and steroid treatment schedule on LH and prolactin release in rats. Rats maintained in either a 14 h light: 10 h dark schedule (LD) or constant illumination (LL) were ovariectomized (Ovx) or ovariectomized and adrenalectomized (Ovx-Adx). Three weeks later at 1000 h, animals received a SC injection of estradiol benzoate (EB 10 mug/100 g BW) or oil. Three days after EB administration, rats were given a 2 mg injection of progesterone (P) or oil at either 0200, 0500, or 0900 h, and were sequentially bled at four-hour intervals until 1700 h. P administered at all three times increased the amplitude of the plasma LH surge and advanced it, though by no more than 4 hours, in LD. In LL, P was more effective in advancing the time of LH release, although peak plasma LH levels were considerably less than those observed in LD. Adrenalectomy increased the sensitivity of Ovx rats to the effects of EB and P on LH release. P administration at either 0200, 0500 or 0900 h advanced prolactin release in EB-primed Ovx and Ovx-Adx in LL and LD, but only in LL did P increase the amplitude of the plasma prolactin surge. The lighting conditions did not alter the effectiveness of P in advancing prolactin release. Our study demonstrates that the light-dark cycle and adrenal steroids interact to synchronize the timing of LH release in rats, but the regulatory mechanism controlling prolactin release is less strictly cued to these environmental factors.

Effect of inhibitors of prostaglandin synthesis on gonadotropin release in the rat.

To study the effect of blockade of prostaglandin (PG) synthesis on gonadotropin release in the rat, inhibitors of PG synthesis were injected by various routes in various experimental conditions. The injection of 5-, 8-, 11-, 14-eicosatetraynoic acid (TYA) into the third ventricle (3rd V) significantly decreased plasma LH of ovariectomized (OVX) rats 1, 2, and 4 h following its injection; however, TYA failed to alter plasma LH in OVX rats when administered as a single sc injection and also failed to prevent the post-castration rise in plasma LH when administered sc once daily for 4 days to short-term OVX rats. None of these treatments altered plasma FSH concentrations. Indomethacin (Id) injected into the 3rd V or implanted into the medial basal hypothalamus (MBH) of OVX rats depressed plasma LH 1--6 h later. This effect was no longer observed 24--72 h following its implantation in the MBH. When different doses of Id were administered as single sc injections to OVX rats, plasma LH titers were depressed 24--32 h later, whereas plasma FSH remained either unaltered or was slightly increased. Similarly, the post-castration rise of plasma LH but not that of FSH in male rats was suppressed by a single sc injection of Id given 6 h before orchidectomy. Id administered acutely iv failed to modify the pulsatile release of LH in OVX rats, but it effectively inhibited this release when injected sc 20--30 h before the initiation of blood collection. Moreover, Id blocked the progesterone-induced LH and FSH release in OVX estrogen-primed rats when given sc 24 h before progesterone, but not when it was injected either sc or iv shortly (2 h) before or shortly after (1--3 h) progesterone treatment. Rats treated with Id showed a decrease in BW 24--32 h afters its sc injection. However, the effects of Id on LH release could not be explained by lack of food intake since fasted controls showed LH titers similar to fed rats. Id did not significantly inhibit the LH release in response to synthetic LH-releasing hormone (LHRH) in OVX rats, but partially blocked the response in OVX estrogen, progesterone-treated (OEP) rats. Surprisingly, in OEP rats, Id appeared to potentiate the FSH release in response to LHRH. The results of this study indicate that inhibitors of PG synthesis administered at high doses can inhibit LH release in the rat and that this effect is mainly due to a direct effect of the drug or drugs on the central nervous systen. Consequently, the results of this study give further support to the hypothesis that PGs play a physiological role in the control of gonadotropin secretion.

Adrenal gland involvement in synchronizing the preovulatory release of LH in rats.

In this study we have demonstrated that acute adrenalectomy (1000 hr proestrus) has no effect on the release of LH on proestrous afternoon. However, chronic adrenalectomy results in the loss of some factor responsible for synchronizing the preovulatory LH surge. Since this investigator has shown previously (15) that progesterone can influence the timing of LH release in ovariectomized and ovariectomized-adrenalectomized animals, it is most likely that adrenal progesterone is involved in synchronizing this event.

THE RESPONSIVENESS OF THE ANTERIOR PITUITARY GLAND TO LUTEINIZING HORMONE RELEASING FACTOR IN RATS EXPOSED TO CONSTANT LIGHT

The responsiveness of the anterior pituitary gland to synthetic luteinizing hormone releasing factor (LH-RF) was tested in rats exposed to constant light. At a dosage of 50 ng LH-RF/100 g body wt the mean maximal increments in plasma LH and FSH were similar to those at 10.00 h of pro-oestrus. The increments in the plasma gonadotrophins at dosages of 500 and 1000 ng LH-RF/100 g body wt did not differ significantly from those at 250 ng LH-RF/100 g body wt. These findings suggest that, in contrast to rats which exhibit regular oestrous cycles, the preovulatory (post-coital) release of LH in rats exposed to constant light may depend almost entirely on the release of a relatively large amount of LH-RF into hypophysial portal vessel blood. Whereas in pro-oestrous animals a relatively small fraction of the readily releasable pool of LH is released during the spontaneous preovulatory surge, in rats exposed to constant light most releasable LH appears to be discharged during the reflex preovulatory surge of this hormone. The concentrations of radioimmunoassayable FSH in blood samples withdrawn before the injection of LH-RF support the view that FSH secretion in the rat is increased by constant exposure to light.

Prostaglandin F2 alpha and LH release in female hamsters.

Worcester Foundation for Experimental Biology, Shrewsbury, Massachusetts 01545, and Department of Biology, Boston University, Boston, Massachusetts 02215, U.S.A. (Received 29th April 1974) Recent studies implicate prostaglandins (PGs) of the E and F series in the release of anterior pituitary hormones (see Carlson, Barcikowski, & McCracken, 1973). Increases in serum levels of LH (Sato, Taya, Tyujo, Hirono & Igarashi, 1974) FSH and prolactin (Sato, Jyujo, Iesaka, Ishikawa & Igarashi, 1974) were observed following a single injection of PG E1, E2 or F2α in rats which were spayed and primed with oestrogen plus progesterone. Intrauterine insertion of a Silastic-PVP implant containing PGF2α has been shown to stimulate the release of LH in rats and hamsters (Saksena, Lau & Chang, 1974). Experiments in which PGs did not affect LH release have also been reported (Chamley & Christie, 1973). Here we report the results of the time sequence of LH

Progesterone supression of LH-releasing hormone-induced stimulation of LH release in rats.

Effects of progesterone on LH release in cycling rats were studied. Doses of 25 mg of progesterone were injected sc into intact adult female rats. Forty-eight hr after the injection, the rats were anesthetized with urethane and a preparation of highly purified LH-RH was injected into the common carotid artery or infused into the pituitary. Control serum LH concentrations in these rats were undetectable both in oil-injected control and progesteronetreated rats. Intracarotid injection of 10 and 50 ng LH-RH into the untreated rats raised serum LH concentrations by 1.5 and 3.6 ng/ml, respectively, 15 min after the injection. The same materials in the progesterone-treated animals increased serum LH by 0.5 and 1.6 ng/ml, respectively. Fifteen min after intrapituitary infusion of saline, 2 ng LH-RH and 10 ng LH-RH, serum LH levels were, respectively, 0.1, 7.6 and 12.5 ng/ml in the control rats and 0, 3.8 and 6.1 ng⁄ml in progesterone-pretreated rats. Factorial analysis of variance indicated that progesterone sig...

Mono- and Indolamines and Control of LH Secretion

To determine the effect of biogenic amines on LH release in rats, blood samples were drawn by cardiac puncture in etheranesthetized animals bearing chronic cannulae in the third ventricle (3rd V) immediately before and 15 min after intraventricular injection of various drugs. In the interim between removal of the 2 blood samples the rats recovered from anesthesia. Plasma LH was measured by radioimmunoassay. Serotonin (5-HT) did not alter plasma LH levels significantly at any stage of 4-day estrous cycles. Norepinephrine (NE) also failed to produce over-all significant changes in plasma LH although there were some positive responses. Dopamine (DA) raised LH to levels as high as 8- or 10-fold above controls (p<.01) in rats on the 2nd day of diestrus (D2) or in proestrus (P). DA proved to be less effective in Dl or estrus (E). In normal males DA raised plasma LH in 5 out of 9 animals (p<.02), whereas NE was ineffective. The effect of DA in D2 and P rats could be blocked by simultaneous 3rd V injection of 30 ...

A 24-hour periodicity in the "LH-release apparatus" of female rats, disclosed by barbiturate sedation.

UNTIL very recently the importance of the nervous system in evoking the ovulatory discharge of gonadotrophin has been recognized in only the few species of animals which fail to ovulate spontaneously. Within recent months, however, several reports from this laboratory (Sawyer, Everett and Markee, 1948, 1949; Everett, Sawyer and Markee, 1948, 1949; Everett and Sawyer, 1949, a, b; Sawyer, Markee and Everett, 1949, 1950) have demonstrated that in the rat, a spontaneous ovulator, neurogenic activation of the hypophysis is essential for the release of ovulating hormone. It was found that either Dibenamine or atropine, agents which block reflexogenic stimulation of the hypophysis in rabbits (Sawyer, Markee and Hollinshead, 1947; Sawyer, Markee and Townsend, 1949), will likewise prevent LH release in rats when injected before certain critical hours during proestrus. In our 4-day cyclic rats these hours are surprisingly uniform, usually between 2 and 4 p.m. Thus, atropine given at 2 p.m. or earlier uniformly prevents LH discharge.