Stimulated LH Release Research Articles

α‐Adrenergic control of gonadotropin secretion in the ewe

The effect of the centrally acting α‐adrenoceptor agonist, clonidine, on plasma LH and FSH was studied in oestradiol‐primed and unprimed ewes and in oestrous ewes. In unprimed anoestrous ewes, clonidine stimulated LH and FSH release after a lag period of 18 h, and noradrenaline intracarotid injection or i.v. infusions immediately stimulated LH release. In oestradiol‐infused anoestrous ewes, clonidine produced either a delay or inhibition of the gonadotrophin surge and noradrenaline i.v. infusion advanced the LH surge. In oestrous ewes treated with clonidine, there was marked delay in the LH surge, but the magnitude of the LH and FSH surges were unaffected. Intravenous administration of α‐adrenoceptor blockers, phentolamine and phenoxybenzamine, blocked the oestradiol‐induced gondotrophin surge in anoestrous ewes. The effect of phenoxybenzamine on gonadotrophin surge was dose dependent in oestrous ewes. Small doses (4 mg/kg i.v.) of phenoxybenzamine delayed the synchronous LH and FSH surges. There was complete blockade of the LH surge and partial blockade of FSH surges in ewes given phenoxybenzamine (8 mg/kg i.v.) before the expected synchronous gonadotrophin surges. After this experiment, the initial rise of plasma progesterone concentrations did not occur until day 6 of oestrous cycle. Administration of phenoxybenzamine before the expected second FSH surge had no effect on the second FSH surge. Gonadotrophin release induced by gonadotrophin‐releasing hormone was attenuated by phenoxybenzamine, but not by clonidine. The results suggest that the LH surge is under α‐adrenergic control and the first FSH surge is under partial α‐adrenergic control, but the second FSH surge is not under α‐adrenergic control. The results also suggest oestradiol modulation of α‐adrenergic receptor action.

Sex difference in LH response to LHRH and DBcAMP and effect of testosterone.

Because luteinizing hormone-releasing hormone (LHRH) stimulates both pituitary cAMP production and LH release, cAMP has been implicated in the action of LHRH on LH release. The effects of LHRH and DBcAMP on LH release were tested in 4-h incubations with pituitary cultures prepared from male or female rats. LH contents in medium and cells were separately determined by radioimmunoassays. LH release in response to 10 nM LHRH was significantly greater in cultures prepared from female rats (female-RPC) than in cultures prepared from male rats (male-RPC), 1,070 and 418% of control, respectively. Addition of DBcAMP (3, 5, or 10 mM) significantly stimulated LH release by female-RPC (212, 206, or 286% of control, respectively) but did not affect LH release in male-RPC. Furthermore, DBcAMP significantly increased the cellular LH content in female- but not in male-RPC. Testosterone pretreatment of female-RPC significantly lowered the LHRH-induced LH release but did not affect the DBcAMP-induced LH release. These data indicate that testosterone may contribute to the sex difference in pituitary LH response to LHRH but not to DBcAMP.

Hypothalamic LH-releasing activity in young and aged intact and gonadectomized rats.

Hypothalamic LH-releasing activity content was measured in young (3-5 mo) and aged (22-26 mo) intact and gonadectomized male and female rats. Hypothalamic extracts (0.25, 0.5 and 1.0 hypothalamus equivalents) from young and aged rats were incubated with untreated hemisectioned rat pituitaries in medium 199. All hypothalamic extract treatments stimulated LH release from the incubated pituitaries. Increased amounts of hypothalamic extracts added to to the incubation medium proportionally increased LH release. There were no differences in LH release stimulated by young or aged hypothalamic extracts from either the intact or gonadectomized groups. In addition serum testosterone concentrations were reduced in the aged male rats and serum LH was lower in aged male and female rats than in the young groups. Although serum LH was increased after gonadectomy in all groups, the increase was of smaller magnitude in the aged rats. These data indicate significant alterations in the responsiveness of the hypothalamus to steroid feedback in the aged rat. Although the hypothalamus contains sufficient LH-releasing activity to stimulate higher levels of pituitary and gonadal endocrine function, aging effects on the neuroendocrine control mechanisms inhibit hypothalamic hormone function.

Effects of a dopaminergic stimulant, amfonelic acid, on anterior pituitary hormone release in conscious rats

The response of plasma LH, Prolactin, GH and TSH levels to systematic administration of a specific central dopaminergic stimulant, amfonelic acid (AFA), by intravenous pulse injection in ovariectomized (OVX) and OVX estrogen-progesterone primed conscious rats has been evaluated. Intravenous injection of 0.2 mg/kg of AFA had no influence on plasma LH concentration until 60 min after injection when it was significantly elevated. Increasing the dose to 1 mg/kg reduced LH titers at 15 and 30 min with a return to preinjection levels by 60 min. AFA produced a dose-dependent decrease in plasma prolactin levels; the decrease occurred as early as 5 min after injection. AFA, both at 0.2 and 1 mg/kg doses, was effective in producing a sharp, dose-related rise in plasma GH levels. By contrast, TSH levels were significantly suppressed by both doses of AFA. Injection of the 1 mg/kg dose of AFA did not modify plasma LH levels in OVX-steroid-primed animals, white producing a comparable effect on plasma prolactin, GH and TSH levels to that observed in OVX animals. The present results indicate that endogenously released DA can have profound effects on pituitary hormone release, inhibiting PRL and TSH discharge, stimulating GH release and either inhibiting or stimulating LH release.

OESTRADIOL RECEPTORS IN THE RAT ANTERIOR PITUITARY GLAND DURING THE OESTROUS CYCLE: QUANTITATION OF RECEPTOR ACTIVITY IN RELATION TO GONADOTROPHIN RELEASING HORMONE-MEDIATED LUTEINIZING HORMONE RELEASE

Specific oestradiol binding to a receptor in nuclear and cytosol fractions of the rat anterior pituitary gland and pituitary responsiveness to gonadotrophin releasing horomone (GnRH) during the oestrous cycle have been studied. To accomplish this, both unoccupied and occupied oestradiol-binding sites in the nucleus and total cell were measured during the oestrous cycle. The concentration of unoccupied and occupied sites and total oestradiol binding in the cytosol fluctuated during the cycle. At pro-oestrus, the concentration of cytosol receptor was diminished by about 40% and replenishment occurred during oestrus. On the other hand, a profound increase is concentrations of cellular and nuclear receptors occurred at pro-oestrus. Administration of GnRH significantly LH release at all stages of the cycle. The maximum stimulation of LH release by GnRH was observed at 13.00 h of pro-oestrus. From these studies, it is concluded that pituitary responsiveness to exogenous GnRH during pro-oestrus parallels the changes in the content of oestrogen receptors in the cytosol and nucleus.

Re-evaluation of the role of catecholamines in control of gonadotropin and prolactin release.

The effect of microinjection of catecholamines into the 3rd brain ventricle on plasma gonadotropins and prolactin (Prl) titers was evaluated in estrogen and progesterone-primed, ovariectomized (OEP) rats which are a particularly sensitive test animal for LH-RH and the responses compared to those obtained in ovariectomized (OVX), unprimed animals. Intraventricular injection of isotonic saline had no effect on plasma gonadotropins or Prl. The injection of dopamine (DA) into the 3rd ventricle elevated plasma LH in the OEP rats at doses of 4 or 20 µg, but the elevation obtained with the 10 µg dose was not significant. A greater effect was obtained with 20 µg doses of both norepinephrine (NE) and epinephrine (E), with E being the most effective of the 3 catecholamines. Apomorphine (APO) also elevated plasma LH following its injection into the 3rd ventricle in the OEP rats. Since these animals were etherized for removal of blood samples and microinjections into the ventricle, a group of animals was used with in-dwelling cannulae in the external jugular vein. In these animals, DA also elevated plasma LH. In OVX animals, the intraventricular injection of DA was without effect on plasma LH, but small transient increases in plasma LH were obtained with 20 µg doses of NE or E. The action of DA in the OEP rat was not prevented by the prior injection of diethyldithiocar-bamate (DDC) which inhibits NE synthesis. Dopamine, apomorphine, and another DA receptor-stimulating drug, Piribedil (ET-495), lowered plasma Prl following their intraventricular injection in all conditions. There were no effects of any of the drug treatments on plasma FSH. It is concluded that intraventricular DA can stimulate LH release in the steroid-primed rat but that NE and E appear to be more effective in this regard. Epinephrine was the most effective catecholamine in stimulating LH release. Dopamine clearly

STIMULATION OF PROSTAGLANDIN ACCUMULATION IN THE RAT ANTERIOR PITUITARY GLAND BY LUTEINIZING HORMONE RELEASING HORMONE IN VITRO

The addition of luteinizing hormone releasing hormone releasing hormone (LH-RH) to cultures of monolayers of rat anterior pituitary cells was shown to increase both the concentrations of prostaglandins E1 and E2 (PGE) in the cells and the release of LH over similar ranges of concentrations of LH-RH (10(-6) to 10(-10) mol/l). The peak concentration of PGE was observed after 2.5 h. The stimulation of the level of PGE in the cells by LH-RH was completely inhibited by two inhibitors of prostaglandin synthetase, which only partially inhibited the stimulation of LH release. Therefore the increased concentration of PGE was not obligatory for the effect of LH-RH on LH release. It was also shown that monobutyryl cyclic AMP stimulated the intracellular concentration of PGE and it is suggested that the stimulation of PGE levels may be mediated by increased levels of cyclic AMP in the cells after the addition of LH-RH.

Effect of Lesions in the Ventral Noradrenergic Tract Produced by Microinjection of 6-Hydroxydopamine on Gonadotropin Release in the Rat1

Noradrenergic innervation to the hypothalamus is provided principally by the ventral noradrenergic tract (VNAT) which carries the axons of noradrenergic neurons whose cell bodies lie in the brain stem. To determine the importance of the VNAT in the stimulation of LH release induced by progesterone in ovariectomized, estrogen-primed rats, 6-hydroxydopamine (6-OHDA), an agent which selectively destroys catecholaninergic neurons, was microinjected bilaterally into this tract, 2 days after priming of the ovariectomized animals with 5 mug of estradiol benzoate, sc. Following microinjection, 2 mg of progesterone was injected sc to provoke LH release. A surge of FSH and LH release occurred 6 h after progesterone in control animals and those injected with the ascorbic acid diluent into the VNAT. Injections of 6-OHDA into the tract completely blocked both the LHP AND FSH surge. Control injections of 6-OHDA into the superior colliculus, the caudate-putamen or the frontal cortex did not alter the release of FSH and LH induced by progesterone. Twenty-four hours after injection of 6-OHDA into the VNAT, there was a slight reduction in norepinephrine content in the anterior hypothalamic area and a significant reduction in the region of the arcuate nucleus and median eminence. In this experiment, 6-OHDA injections into the VNAT blocked not only the FSH and LH release induced by progesterone but also the increase in serum prolactin which was present in control animals. In normal females, injections of 6-OHDA into the VNAT blocked the proestrous discharge of LH and partially blocked that of FSH. It is concluded that acute interruption of the VNAT induced by a 6-OHDA can block not only the stimulation of FSH and LH induced by progesterone, but also the preovulatory discharge of gonadotropins. The results suggest that increased impulse traffic in the VNAT on the afternoon of proestrus may be involved in induction of the proestrous gonadotropin surge.

Induction of luteinizing hormone release by gonadal steroids in the ovariectomized domestic hen.

The ability of intramuscular injections of gonadal steroids to exert a positive feedback action on LH secretion was investigated in the ovariectomized hen. Plasma LH was measured by radioimmunoassay. Single injections of progesterone (dose range: 0.05-10 mg/kg) or oestradiol benzoate (dose range: 0.01-1 mg/kg) did not result in an increase in plasma LH concentration. After priming with 0.1 mg oestradiol benzoate/kg on alternate days for 7 days and with 0.5 mg progesterone/kg on days 5, 6 and 7, a single injection of progesterone on day 8 (dose range: 0.1-2 mg/kg) caused the plasma LH concentration to start increasing after 15 to 30 min. Peak LH concentration was reached around 1.5-2 h after injection. The magnitude of LH response to progesterone was dose related. In contrast, a single injection of oestradiol benzoate (dose range: 0.01-1 mg/kg) failed to stimulate LH release in the oestrogen-progesterone primed ovariectomized (O-P-OVX) hen. A single injection of testosterone (dose range: 0.1-2.0 mg/kg) failed to stimulate LH release in ten out of 12 O-P-OVX hens. A small increase in LH secretion was observed in the two remaining birds. When oestrogen or progesterone was omitted from the priming schedule, a LH positive feedback response to a single injection of progesterone was not observed. Increasing or decreasing the mount of oestrogen or progesterone in the priming schedule modified the LH response to a single injection of progesterone on the day following the last priming injection. This suggested that a critical oestrogen to progesterone ratio was required to prime the LH positive feedback mechanism. It is suggested that, in the hen, the release of LH is facilitated by the positive feedback effect of a combination of oestrogen and progesterone in a two-phase process. The first is the priming phase, which depends on the presence in the blood of oestrogen and progesterone; the second is the ind .uctive phase, which depends only on an incremental change in plasma progesterone concentration. Oestrogen is not involved in the induceive phase.

Further studies on prostaglandin E 2 (PGE 2)-induced gonadotropin release: Comparison with the effect of 15-methyl PGE 2, PGAs, PGBs and prostaglandin endoperoxide analogs

It is known that PGE 2 is a potent stimulus of LH release. To determine if the effect of PGE 2 could be enhanced and/or prolonged by retarding its metabolic degradation, a derivative, 15-methyl PGE 2 (15-E 2) which is more slowly degraded than the natural compound was injected intravenously (i.v.) at various dose levels or into the third ventricle (3rd V) of ether-anesthetized, ovariectomized, estrogen (OVX, Eb)-treated rats and its effect on gonadotropin release was compared with that of PGE 2. Both PGs injected i.v. were equally effective in increasing plasma LH and maintaining the elevated levels, although 15-E 2 induced a larger and more sustained increase in plasma FSH than PGE 2. By contrast, 3rd V PGE 2 was clearly more effective than 3rd V 15-E 2 in releasing LH and to a lesser extent, FSH. The effect of 15-E 2 on LH was similar to that produced by 3rd V PGE 1 injected at a similar dose. However, its effect on FSH was greater than that of PGE 1. To evaluate the effect(s) of prostaglandins of the A and B series on gonadotropin release, PGA 1, PGA 2, PGB 1 or PGB 2 were injected intraventricularly in OVX, Eb-treated rats. PGBs were injected into conscious, free-moving rats. PGA 2 or PGB 2 increased plasma LH concnetrations although much less effectively than PGE 2. Third V PGA 1 or PGB 1 were ineffective. The 3rd V injection of two cyclic esters (U-44069 and U-46619), stable analogs of the PG endoperoxide PGG 2 and PGH 2, induced a small, transient increase in LH levels and did not alter plasma FSH in conscious, free-moving animals. PGE 2 injected intraventricularly at a similar dose was demonstrated to be much more potent than the analogs in stimulating LH and FSH release. The results indicate that: 1) 15-E 2, in spite of its described long-lasting activity, does not appear to be more potent than the natural compound in releasing LH, although when injected i.v., it appeared to induce a more sustained increase in plasma FSH; 2) although PGA 2 and PGB 2 can also act centrally to stimulate LH release, their low potency suggests that this is a pharmacological effect; and 3) the two analogs of PG endoperoxides tested proved to be poor stimuli for gonadotropin release. The significance of these findings is discussed.

Plasma LH and testosterone in Zebu crossbred bulls after exposure to an estrous cow and injection of synthetic GnRH

Plasma hormone levels were examined in 4 mature Zebu bulls of normal libido (HL) and 4 which were sexually inactive (LL). When used in an artificial insemination programme the 8 bulls had similar fertility. Basal levels of LH and testosterone (T) estimated from 8 sequential blood samples at 30 minute intervals were not different in HL and LL bulls. Exposure of the animals to an estrous cow did not stimulate LH release. Following sexual stimulation plasma T levels actually decreased by an average (±S.E) of 2.9 (±1.9) ng/ml in the HL group and increased by 3.9 (±1.6) ng/ml in the LL group. An injection of 1 mg GnRH (Hoechst) caused LH release of similar magnitude in HL and LL bulls. The elevation of plasma T which followed GnRH injection was significantly larger in HL bulls. Low libido was not associated with a deficiency of basal LH or T, nor with the ability of the pituitary to respond to GnRH.

Effects of progesterone and synthetic luteinizing hormone releasing hormone on the release of luteinizing hormone during sexual maturation in the hen (Gallus domesticus).

Single intramuscular injections of 0-5 mg progesterone/kg resulted in increased LH secretion in laying hens but not in pullets with completely undeveloped sexual organs. Injections of the steroid were first able to stimulate LH release 8-10 weeks before the onset of lay when the comb, ovary and oviduct had started to grow and basal plasma LH concentrations were beginning to rise. At this time, injecitons of 10 mug synthetic LH-RH/kg resulted in an incremental change in plasma LH levels of around 26 ng/ml. A similar incremental change was observed after giving the same dose of LH-RH to pullets with no signs of sexual development. Three to four weeks before the first eggs were laid, basal plasma LH levles started to fall, the pituitary became progressively more insensitive to synthetic LH-RH and injections of 0-5 mg progesterone/kg resulted in a reduced LH response. Ten mug LH-RH/kg caused incremental changes in blood levels of LH of less than 5 ng/ml. The final stage of sexual maturation occurred during the week before the onset of lay and was characterized by a rapid growth of large yolky ovarian follicles and a further fall in the sensitivity of the pituitary to synthetic LH-RH. However, injections of 0-5 mg progesterone/kg resulted in a prolonged release of LH. These observations are discussed in relation to the maturatio of the positive feedback mechanism by which progesterone stimulates the secretion of LH.

Stimulation of LH release and ovulation in the rat by cutaneous application of luteinizing hormone-releasing hormone (LH-RH) in dimethyl sulfoxide (DMSO).

The efficacy of cutaneously applied luteinizing hormone releasing hormone (LH-RH) in stimulating LH release in the chronically ovariectomized, estrogen/progesterone-blocked rat and ovulation in the chlorpromazine-blocked, proestrous rat was investigated. Following the cutaneous application of 25 or 100 mug of LH-RH in 100% dimethyl sulfoxide (DMSO), serum LH rose to a peak at 1 hr, then declined toward basal levels in the ensuing 3 to 4 hr. LH-RH applied cutaneously in either 100% DMSO or 0.9% NaCl was also capable of inducing ovulation in the chlorpromazine-blocked, proestrous rat; however, LH-RH in 0.9% NaCl did not yield a linear log-dose-response relationship, therefore a valid ED50 potency ratio for DMSO/0.9% NaCl could not be estimated. Nonetheless, 0.9% NaCl was a considerably less effective cutaneous vehicle than DMSO. Cutaneous application of LH-RH in DMSO in doses of 100, 50, 25, 10, 5, 2.5 and 1 mug induced ovulation in 100%, 100%, 90%, 73%, 30%, 10% and 0% of the rats, respectively. When the percent ovulation response was transformed to probits and plotted against the logarithm of the LH-RH dose an approximately linear log dose-response was obtained; the same relationship also held true for ovulation induction following sc LH-RH administration. In turn, the ED50's of these two parallel dose-response curves yielded a potency ratio estimate (sc/cutaneous) of 0.025, suggesting that 2.5% of the cutaneously applied LH-RH dose was absorbed through the skin in a biologically active form. These data indicate that DMSO privdes a convenient cutaneous vehicle for the administration of LH-RH.

Prostaglandin administration to pregnant rats: effects on pituitary-target gland systems of mother, fetus and neonate (38512).

Acute administration of PGE-1 in graded doses (0.25-1.0 mg) to pregnant rats in late gestation (21st day) induced significant release of TSH, prolactin and LH from the maternal, pituitary. Plasma levels of PRL and TSH were elevated (three- to fivefold) in cesarean sectioned mothers given 4-5 sc injections of PGE-1; higher doses also stimulated LH release. Comparable increases in blood TSH and PRL levels were also found in their newborn but no indication of enhanced hormone release from the fetal hypophysis was noted. Histologic alterations were observed in the ovary (luteal cell hypertrophy, cytopasmic clearing, nuclear condensation, sinusoidal distension) of mothers receiving PGE-1 treatment. Thyroidal radioiodine accumulation in mother, fetus and neonate were usually decreased whereas thyroid: blood radioactivity ratios were consistently incrased. It is concluded that PGE-1 treatment of th pregnant rat near term stimulates release of hormones from the pituitary in mothers (TSH, LH, PRL) and in their newborn (TSH, PRL). The results also strongly suggest that PGE-1 administration may induce morphologic and functional changes in target endocrines (ovary, thyroid) by direct and separate actions.

Transport of LRF from CSF to hypophysial portal and systemic blood and the release of LH.

The capacity of the median eminence to transport LRF from CSF to hypophysial portal blood and the efficacy of intraventricularly and intravenously administered LRF in releasing LH were studied. Ten to 15 min after 125 ng LRF was injected intraventricularly, LRF was detected in portal blood. The maximal rate of transport ranged from 35 to more than 200 pg'min. The rates of transport were much less following the administration of 25 or 5 ng LRF. When these same quantities of LRF were injected intraventricularly into rats with intact pituitary glands, plasma LH levels increased in proportion to the dose of LRF. The releasing action of LRF was long, and 120 min after the administration of 125 ng LRF, the concentration of plasma LH was 40- to 50-fold greater than the control level. Intravenous injection of 5, 25, or 125 ng LRF caused corresponding increases in LH release. Intravenously administered LRF stimulated LH release slightly faster than did LRF given intraventricularly, but the effect of intraventricul...

Effects of hormone treatment and age on the stimulation of rat anterior pituitary adenylate cyclase and cyclic adenosine 3′,5′ monophosphate by hypothalamic extract

Crude ovine hypothalamic extract in vitro significantly stimulated adenylate cyclase activity and LH release by pituitary gland obtained from newborn rats (0.25–0.5 days old) and increased cyclic adenosine 3′,5′-monophosphate (cyclic AMP) in 2-day-old rats. In adult rats, the stimulation of adenylate cyclase activity and cyclic AMP formation, but not LH release, induced by hypothalamic extract was inhibited by adrenalectomy. In vivo administration of pharmacologic doses of 1 mg dexamethasone asd 100 μg thyroxine for 1 day markedly reduced the effect of 0.2 mg/ml but not 1 mg/ml hypothalamic extract on cyclic AMP concentrations. The action of the latter dose of hypothalamic extract on cyclic AMP was inhibited by injection of dexamethasone and thyroxine for 3 days, while the stimulation of LH release was preserved. Such dissociation between activation of the adenylate cyclase-cyclic AMP system and LH release suggests that cyclic AMP formation may not be essential for increased release of LH. Adrenalectomy did not inhibit stimulation of adenylate cyclase activity or cyclic AMP formation caused by prostaglandin E 1 (PGE 1). Hypothalamic extract or PGE 1 added to intact pituitary in vitro increased protein kinase activity and decreased the protein binding of exogenous cyclic AMP, reflecting the increased generation of endogenous cyclic AMP.

Role of estrogen in the restoration of LH release following stimulation of partially deafferented hypothalamus in rat

Stimulation of LH release following electrochemical stimulation (EC) of median eminence-arcuate region (ME-ARC) during various stages of 5-day estrous cycle of rat has been studied. On day 2 post-ovulation (diestrus II), when the vaginal smear consisted of leucocytes, elevations in plasma LH as a result of ME-ARC stimulation were minimal. With the change in vaginal smear to nucleated epithelial cells on day 3 (proestrus I) and cornified cells on day 4 (proestrus II) post-ovulation EC stimulation induced significantly higher elevations in plasma LH than those obtained following stimulation on diestrus II. To determine whether neural links between medial preoptic area and ME-ARC are essential during the period in which the marked changes in sensitivity of ME-ARC to EC stimulation occur, the anterior hypothalamus was partially deafferented (AAD) in rats at various stages of the estrous cycle.Plasma LH levels following EC stimulation of ME-ARC at 18.00 h of proestrus I were assessed in these AHD rats. LH levels were found to be correlated with cell types present in the vaginal smear at the time of EC stimulation. Nucleated epithelial cells were present at the time of stimulation in rats deafferented at 09.00 h of proestrus I or 18.00 h of diestrus II and in 5/9 rats at 08.00 h of diestrus II similar to the control rats in which sham AHD was performed at 09.00 h of fiestrus II or of proestrus I. Elevations in plasma LH after stimulation in these rats were comparable to those observed in sham AHD control rats. Quite different results were obtained when AHD was performed at 17.00 h of diestrus I or at 08.00 h of fiestrus II (4/9 rats). Vaginal smear consisted of leucocytes; and slight elevations of plasma LH after stimulation of ME-ARC were detected. However, administration of estradiol benzoate (5 μg/rat) 12 h after AHD at diestrus I not only induced cornification of vagina but also restored the plasma LH values to those obtained following stimulation of ME-ARC of intact or sham AHD control rats. These results indicate that maximal LH release following ME-ARC stimulation of deafferented rats requires estrogen priming.

Physiological studies on the LH- and FSH- releasing hormone its analogues, and antisera.

Literature on the effects of luteinizing hormone-release hormone (LH-RH) and its analogs and antisera is reviewed. LH-RH is a polypeptide isolated from the porcine hypothalamus with a structure of (pyro) Glu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2. In rats LH-RH increases the production of LH and follicle stimulating hormone (FSH) stimulates spermatogenesis and follicular development and induces ovulation. LH-RH stimulates ovulation and the release of LH and FSH in sheep rabbits and hamsters. LH-RH stimulates LH release in pigs and cattle induces LH release and ovulation in some species of fish cand causes premature ovulation in chickens. The induced increases in serum LH and FSH in monkeys is not as great as that in humans. The administration of sex steroids amplifies the pituitary response to LH-RH. Estrogens inhibit the rise in FSH though it can augment the rise of LH in response to LH-RH whereas dihydrotestosterone has the inverse effect. The half-life of LH-RH is about 6 minutes in the rate and 4 minutes in humans. In both animals and humans LH-RH appears to stimulate fertility. In rabbits immunization with LH-RH caused severe testicular atrophy in rats. In rats the administration of antisera against LH-RH suppressed the preovulatory surge of LH and FSH and blocked ovulation. Several synthesized analogs of LH-RH such as desHis2desGly10-LH-RH-ethylamide blocked the in vivo response to LH-RH in rats and inhibited ovulation in rats and rabbits. The results to data emphasize the possibility of developing effective polypeptide contraceptive agents.

The effects of hypothalamic lesions on the release of gonadotropins and prolactin in response to estrogen and progesterone treatment in female rats.

Plasma gonadotropins and prolactin were measured in rats with hypothalamic lesions. In ovariectomized females estrogen lowered plasma FSH and LH and elevated plasma prolactin. Lesions in the median eminence of ovariectomized rats which lowered plasma gonadotropins and elevated plasma prolactin prevented these effects of estrogen. The ability of progesterone to stimulate FSH and LH release in ovariectomized, estrogenprimed rats was also eliminated by these lesions. Lesions in the suprachiasmatic region which induced constant estrus in animals with intact ovaries failed to block the inhibitory effect of estrogen on gonadotropin release and the rise in prolactin evoked by estrogen still occurred. The stimulation of LH release by progesterone was blocked by these lesions, whereas the stimulation of FSH release was unimpaired. The results are discussed in terms of the sites of the feedback actions of gonadal steroids. (Endocrinology 91: 1404, 1972)

Release of LH during treatment with purified sheep FSH without signs of adequate follicular maturation in women.

Four amenorrhoeic women were treated with a purified sheep fsh preparation. During treatment, plasma progesterone, oestradiol and lh concentrations were measured every 24 or 48 hr. In all the women, an lh peak was found during treatment, even though in three of these there was no evidence of adequate follicular maturation, as assessed by plasma oestradiol levels. These results indicate that a peak of plasma oestradiol need not necessarily be the unique stimulus for lh release and the possibility that fsh in humans can stimulate lh release directly through a short loop feedback mechanism should not be disregarded. Recent studies on plasma oestradiol and lh levels have supported the growing view that a rise in