Control Of Luteinizing Hormone Release Research Articles

Perspectives on Endogenous Opioids in Birds.

The present review summarizes the state of knowledge of endogenous opioids in birds. Endogenous opioid peptides acts in a neuromodulatory, hormonal and paracrine manner to mediate analgesic and other physiological functions. These peptides act through specific G-protein coupled receptors. Opioid receptors consist of a family of four closely-related proteins. The three types of opioid receptors are the mu (MOR or μ), delta (DOR or δ), and kappa (KOR or κ) opioid receptor proteins. The role of the fourth member of the opioid receptor family, the nociceptin or orphanin FQ receptor (ORL), is not clear. The ligands for opioid receptors are: β –endorphin (MOR), Met- enkephalin, Leu-enkephalin (DOR) and dynorphin (KOR), together with probably endomorphins 1 and 2. In spite of long history of research on endogenous opioid peptides, there are no studies of endogenous opioids per se in wild birds and few in poultry species. β-endorphin is present in all birds investigated and there is close agreement between the structures of β-endorphin in different birds. Plasma concentrations of β-endorphin are increased by ether stress in geese. There is evidence that β-endorphin plays a role in the control of luteinizing hormone release in chickens. Met-enkephalin is present in tissues such as the retina, hypothalamus, pituitary gland, and adrenals together with circulation of birds. Stresses such as crowding and withholding water increase circulating concentrations of Met-enkephalin in chickens. The structures of chicken dynorphin A and B have been deduced from cDNA. What is missing are comprehensive studies of plasma concentrations and expression of the full array of endogenous opioids in multiple avian species under different situations. Also, what is not known is the extent to which circulating or locally released or intra-cellular Met-enkephalin influence physiological process in birds. Thus, there is considerable scope for investigation of the physiology of endogenous opioids in birds.

Serotonin, GnRH-A, and dopamine interaction in the control of in vivo luteinizing hormone release in Prussian carp (Carassius gibelio Bloch) at the time of gonad recrudescence

The effects of serotonin (5-HT), GnRH analogue (D-Ala6 LHRH, GnRH-A) and dopamine antagonist - pimozide (PIM), on luteinizing hormone (LH) release in mature Prussian carp female (Carassius gibelio Bloch) were examined at the time of gonad recrudescence. Fish were intraperitoneally injected with 5-HT (10 mg/kg), GnRH-A (20 μg/kg) or PIM (5 mg/kg) or the combinations: 5-HT+GnRH-A, 5-HT+PIM, 5-HT+GnRH-A+PIM. Before the injection and 3, 6, 12 or 24 h after treatment blood samples were collected for LH levels determination by ELISA method. The analysis of LH concentrations, expressed as the percentage of pre-treatment, showed that serotonin alone had no influence on the spontaneous LH release, however the additive effects of serotonin and GnRH-A was observed. Serotonin potentiated the GnRH-A-stimulated LH release and potentiated also the effect of PIM. Extremely strong response to PIM and also to the combination with GnRH-A masked the participation of serotonin in the process of LH release in fish with recrudescing gonads. The interaction of serotonin GnRH-A and PIM in the control of LH release is discussed.

Estrogen Biphasically Modifies Hypothalamic GABAergic Function Concomitantly with Negative and Positive Control of Luteinizing Hormone Release

The principal role of estrogen is its control of the female ovulatory cycle via negative and positive feedback on gonadotropin secretion. However, a detailed, cohesive picture of how the steroid specifically regulates the excitability of hypothalamic neurons involved in the central control of gonadotropin secretion is still emerging. Here, we used an ovariectomized female guinea pig model to test the hypothesis that estrogen acts on GABAergic neurons in the preoptic area (POA) to elicit a biphasic profile of luteinizing hormone (LH) secretion. Intracellular electrophysiological recordings revealed that estradiol benzoate (EB; 25 microgram, s.c.) decreased the hyperpolarizing response of GABAergic neurons to the GABA(B) receptor agonist baclofen 24 hr after treatment. This effect of GABA(B) receptor stimulation in unidentified POA neurons was still depressed 42 hr after EB administration. By the use of a ribonuclease protection assay, however, EB reduced glutamic acid decarboxylase mRNA expression 42 hr but not 24 hr after its administration. Thus, estrogen attenuated the autoinhibition of GABAergic POA neurons during the initial LH suppressive (i.e., negative feedback) phase and subsequently reduced GABAergic function during the LH surge (i.e., positive feedback). These studies demonstrate that the effects of estrogen on hypothalamic GABAergic neurons coincide with the inhibitory and stimulatory actions, respectively, of the steroid on LH secretion. Furthermore, the data provide novel insights into the mechanism by which estrogen regulates hypothalamic GABAergic neurons, which are critical for the biphasic modulation of LH release observed over the course of the female ovulatory cycle.

Plasma levels of luteinizing hormone during hyperprolactinemia: response to central administration of antagonists of corticotropin-releasing factor.

Since high concentrations of prolactin (PRL) enhance the hypothalamic release of corticotropin-releasing factor (CRF), and CRF decreases the hypothalamic secretion of luteinizing hormone (LH)-releasing hormone (LHRH), it could be that CRF is involved in the suppressed secretion of LH during hyperprolactinemia. The aim of this study was to explore this possibility in hyperprolactinemic male rats. Hyperprolactinemia, induced by insertion of 3 pituitary glands under the kidney capsule, decreased plasma LH levels by 68% and caused a 2-fold increase in plasma corticosterone. Intracisternal administration of the CRF antagonist alpha-helical CRF(9-41) induced both in pituitary-grafted rats and in normoprolactinemic controls a 2 to 3-fold increase of LH in the plasma sample taken 1 h after injection of alpha-helical CRF(9-41). Plasma levels of LH in pituitary-grafted rats were 2-3 times higher during intracerebroventricular infusion for 7 days with CRF antiserum than during saline infusion. Furthermore, after infusion of CRF antiserum for 7 days into the lateral brain ventricle plasma LH levels had increased by 270% in normoprolactinemic male rats. These results indicate that hypothalamic CRF is involved in the control of LH release in male rats. To further investigate whether CRF is involved in the effect of PRL on LH secretion, we infused PRL, alone or together with CRF antiserum, for 7 days into the lateral brain ventricle of normoprolactinemic male rats. After 7 days of PRL infusion, LH levels had decreased by 45%, whereas plasma corticosterone was 150% higher. This action of PRL on LH and corticosterone was prevented when besides PRL also CRF antiserum was infused.(ABSTRACT TRUNCATED AT 250 WORDS)

Different effects of unilateral and bilateral lesions of the dorsal raphe nucleus on puberty and first ovulation

The effects of unilateral and bilateral electrolytic lesions of the dorsal raphe nuclei (DRN) of 30-day-old rats, on the spontaneous and induced ovulation, were analyzed. The bilateral lesion and the lesion on the right side of the DRN delayed the age of first vaginal estrous. None of the animals with bilateral lesion on the DRN ovulated on the day of first estrous (0/8 vs. 12 15 , p < 0.05). The ovulation rate in animals with unilateral lesion on the DRN was similar to sham-operated animals, but the number of ova shed by ovulating animals increased in the ovary ipsilateral to the lesion (lesion on right DRN, right ovary: 6.5 ± 0.5 vs. 4.5 ± 0.4; lesion on left DRN, left ovary: 6.4 ± 0.3 vs. 4.2 ± 0.4, p < 0.05). By the injection of human chorionic gonadotropin, ovulation was restored in rats with a bilateral lesion on the DRN (3/5 vs. 0/8, p < 0.05). The present results suggest that serotoninergic input to the hypothalamus, arising from the DRN, exerts a facilitatory influences on the control of luteinizing hormone release. To explain the increase in the number of ova shed by the left and right ovary, observed in rats with an ipsilateral lesion, we suggest the existence of a neural connection between the DRN and the ovary.

Inhibitory effects of the new bombesin receptor antagonist RC-3095 on the luteinizing hormone release in rats.

The effects of bombesin receptor antagonist RC-3095 and gastrin-releasing peptide [GRP (14-27)] on basal luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone levels, as well as on the release of LH and FSH in response to LH-releasing hormone, were studied in normal and castrated male rats. We also examined the release of LH and FSH after intracerebroventricular injection of RC-3095 under different types of anesthesia (urethane, sodium pentobarbital, Metofane). Following injection of 10 micrograms RC-3095 into the lateral brain ventricle, serum LH levels were rapidly and significantly (p < 0.001) lowered. This effect lasted for at least 60 min and was not affected by the type of anesthetic used. Serum FSH levels were not affected by intracerebroventricular administration of RC-3095 or GRP (14-27), indicating different central control mechanisms between LH and FSH release. The suppressive effect of RC-3095 on LH release could be completely prevented by prior intracerebroventricular administration of GRP (14-27) at a dose of 1 micrograms, but intravenous administration of either peptide RC-3095 or GRP (14-27) did not change the basal levels of LH, FSH, and testosterone. The pituitary LH response to LH-releasing hormone was also not modified by intravenous administration of RC-3095. These results indicate that bombesin-like peptides might be involved in control of LH release from the pituitary by an action on the CNS which is mediated by specific bombesin receptors.

Interactions between neuropeptide Y, luteinizing hormone-releasing hormone and estradiol in the control of luteinizing hormone release from cultured ovine pituitary cells

This study used pituitary cells in culture firstly to test the hypothesis that NPY may augment the pituitary LH response to LHRH and secondly to determine whether this interaction is dependent on the presence of estradiol. LHRH (10(-10)-10(-6) M) caused a significant increase in LH secretion from dispersed ovine pituitary cells maintained in culture for six days, a response which was enhanced when cells were pretreated for three days with 4 x 10(-11) M estradiol. NPY 10(-10)-10(-6) M) had no effect on basal LH release from ovine pituitary cells maintained either in the presence or absence of estradiol. NPY (10(-10) and 10(-8) M) also had no effect on LHRH-stimulated LH release either in the presence or absence of estradiol. These results substantiate previous observations that physiologically relevant concentrations of estradiol enhance the LH response to LHRH in cultured ovine pituitary cells. However, in contrast to experiments carried out using rat pituitary cells in culture, the present data provide no evidence to support the hypothesis that NPY alone interacts with LHRH in the control of LH secretion from the ovine pituitary gland.

Role of Gamma-Aminobutyric Acid in the Zona incerta in the Control of Luteinizing Hormone Release and Ovulation

gamma-Aminobutyric acid (GABA) neurones are present in the zona incerta (ZI) where other systems have been shown to influence gonadotrophin release. This report investigates the effect of GABA agents in the ZI on ovulation and luteinizing hormone (LH) release. In intact females under Saffan anaesthesia, bilateral stereotactic injections into the ZI of two GABA transaminase inhibitors [amino(oxy)acetic acid and gamma-acetylene GABA] on the morning of pro-estrus or two GABA agonists on the afternoon of pro-estrus inhibited ovulation. The selective GABA B agonist baclofen was effective at 0.05 nM; muscimol, a mixed GABA A and B agonist, was 50-fold less potent, while the selective GABA A agonist isoguvacine had no effect at 500 nM. Administration of baclofen at 0.05 and 5 nM into the ZI significantly reduced plasma LH concentration in untreated ovariectomized rats and also prevented the rise in LH normally induced in ovariectomised rats primed with 5 micrograms oestradiol benzoate (OB) plus 0.5 mg progesterone. In ovariectomised rats primed with 5 micrograms OB alone, administration of the selective GABA A antagonist bicuculline (200 and 260 pg/side) had no effect on plasma LH, while the GABA B antagonist phaclofen (10 pg/side) stimulated a rise in plasma LH, 40 and 60 min after injection. These results indicate that GABA activity in the ZI exerts an inhibitory effect on LH release and ovulation and this is preferentially exerted via GABA B receptors.

Opioid modulation of tonic luteinizing hormone release in ovariectomized dairy cows.

A possible role of endogenous opioid peptides (EOP) in regulating the release of luteinizing hormone (LH) in the absence of ovarian influence was investigated. Experiments were conducted on three lactating Holstein-Friesian dairy cows, 20-27 days after ovariectomy. The cows were bled before and after a single intravenous (i.v.) injection of either 250 mg of naloxone (EOP antagonist) or 300 mg of morphine (EOP agonist) or a combination of the two in Experiments 1, 2 and 3, respectively. The mean and basal LH concentrations and the LH pulse frequency and amplitude were compared before and after each treatment in each cow. Naloxone induced an immediate rise in LH concentration by 60-300% above the preceding baseline values. This rise lasted for 15-30 min in each cow, after which the normal rhythmic LH release continued. One cow (A) suffered discomfort and respiratory distress 15-25 min after naloxone administration and the mean and basal LH concentration dropped significantly. Morphine significantly reduced the mean LH concentration by decreasing the number and amplitude of LH pulses and the basal LH values in two cows, although the decrease in one was not significant. The mean LH concentration in each cow remained unaffected by the combined treatment of morphine and naloxone. In conclusion, the elevation of LH concentration by naloxone, the suppression of LH release by morphine and the reversal by morphine and naloxone of each other's effects suggest that EOP could be involved in the control of LH release in cows in the absence of ovarian influence.

Opioidergic control of luteinizing hormone release in the female rabbit: influence of ovariectomy and steroid replacement on pulsatile secretion.

The influence of ovariectomy and steroid replacement on naloxone-induced changes in pulsatile secretion of luteinizing hormone (LH) in the female rabbit was examined. Blood samples were taken every 5 min through an indwelling catheter in the rabbit ear artery, and plasma was stored until assayed for LH by established radioimmunoassay procedures. In the intact animal, saline injection had no effect on LH secretion. Although naloxone (10 mg/kg) caused a 7-fold increase in mean LH pulse amplitude by 30 min after injection, this increase was not statistically significant because 5 of 11 animals did not respond. In animals ovariectomized 48 h previously, naloxone significantly increased LH concentration by 194% at 23 min after injection. When long-term ovariectomized rabbits were treated with estradiol benzoate and then were given naloxone, no significant increase in LH was observed, although many animals did respond. Treatment of long-term ovariectomized rabbits with 1 microgram estradiol benzoate and 100 micrograms progesterone or 1 mg testosterone propionate on Days 1 and 3 and naloxone on Day 4 resulted in a significant increase in LH 19-24 min later. Although there was an increase in pulse amplitude, no change was detected in pulse frequency after naloxone. These data suggest that the hypothesis of steroid-opioid coupling in the control of LH secretion is not applicable to the female rabbit.

Subfornical organ connections with septal neurons projecting to the median eminence.

We have examined the effect of electrical stimulation in the subfornical organ (SFO) on the activity of neurons in the medial septum and diagonal band of Broca (MS-DBB) which project to the median eminence in the rat. Previous studies have suggested that septal neurons with such projections are luteinizing hormone releasing hormone neurons. Extracellular single-unit recordings were obtained from 69 neurons in the MS-DBB which were antidromically identified as projecting to the median eminence. Electrical stimulation (100-400 microA) in the SFO resulted in a relatively short-latency (22.8 +/- 0.8 ms), short-duration (9.2 +/- 0.8 ms) activation of 85% of 41 antidromically identified MS-DBB neurons tested. One neuron was inhibited by SFO stimulation, while the remaining 12% were unaffected. Stimulation in nearby regions, including the hippocampal commissure and paraventricular nucleus of the thalamus, failed to elicit a similar excitatory response from 19 identified MS-DBB neurons. These results identify a neuronal pathway between the SFO and septal neurons which project to the median eminence, supporting a possible role for the SFO in the control of luteinizing hormone releasing hormone release and hence gonadotropin secretion.

Suppressive effect of dynorphin-(1–13) on luteinizing hormone release in conscious castrated rats

The effect of intraventricular administration of dynorphin-(1–13) of luteinizing hormone (LH) release was studied in castrated conscious rats. The administration of 5 μg of dynorphin-(1–13) into the lateral ventricle inhibited LH secretion. Intravenous administration of naloxone blocked this suppressive effect of dynorphin on LH release. These results suggest a possible role of dynorphin, in addition to β-endorphin and Met 5-enkephalin, in the control of LH release in male rats.

The effect of Λ 9-tetrahydrocannabinol on the positive and negative feedback control of luteinizing hormone release

The principal psychoactive component of marihuana, Λ 9-Tetrahydrocannabinol (THC), decreases serum LH levels when given to ovariectomized rats at a dose of 10 mg/kg. This same dose of THC blocks both the estrogen and progesterone mediated positive feed-back release of LH. The steroid-induced LH surge, when blocked by THC, reappears 24 h later. The positive feedback release of LH should serve as a suitable model to study the mechanism of action by which THC blocks the ovulatory LH surge.

Rapid Direct Effects of Castration and Androgen Treatment on Luteinizing Hormone-Releasing Hormone-Induced Luteinizing Hormone Release in the Phenobarbital-Treated Male Rat: Examination of the Roles Direct and Indirect Androgen Feedback Mechanisms Might Play in the Physiological Control of Luteinizing Hormone Release*

Adult male rats, given phenobarbital (PB) to suppress their endogenous LH-releasing activity, were used to test whether orchidectomy and dihydrotesterone (DHT) treatment and withdrawal could act acutely to modify the pituitary LH release response to exogenous LHRH infusion. When LHRH was infused at a constant rate of 15 or 45 ng/h beginning immediately after orchidectomy, castrates and sham-castrated controls responded similarly for up to 18 h. However, when the LHRH infusion rate was abruptly changed from 15 to 45 ng/h 4 h postoperatively, castrates developed greater serum LH levels than uncastrated controls. Castration (the withdrawal of testicular feedback signals) appeared to have increased the ability of the pituitary to respond to an increment in the LHRH infusion rate. This effect of orchidectomy was reduced in rats given DHT by sc implantation at the time of castration, using doses of DHT equal to or less than those needed to prevent the orchidectomyinduced increase in circulating LH in the absenc...

Pituitary responsiveness to a single injection of synthetic luteinizing hormone releasing hormone before and after the natural preovulatory plasma luteinizing hormone peak in the sheep.

Department of Physiology and Environmental Studies, University of Nottingham School of Agriculture, Sutton Bonington, Loughborough, LEI2 5RD (Received 14 May 1976) Peaks of immunoreactivity detected by the luteinizing hormone releasing hormone (LH-RH) radioimmunoassay of Jeffcoate, Fraser, Gunn & Holland (1973) occur in the jugular venous blood of the sheep before, during and after the luteinizing hormone (LH) peak at oestrus. Those occurring after the LH peak are not associated with further increases in the LH concentration (Crighton, Foster, Holland & Jeffcoate, 1973). If these immunoreactivity peaks give an indication of LH-RH release from the hypothalamus then changes in pituitary responsiveness must be important in the control of LH release. In the present experiment the responsiveness of the sheep pituitary gland to a single injection of 50 μg synthetic LH-RH was tested both before and after the natural preovulatory LH release. Each ewe (Clun Forest) was given a single i.v. injection

Interaction of progesterone, GnRH and estradiol in the control of LH release in castrate heifers.

Thirteen ovariectomized heifers were randomly divided into two groups for each of three experiments. In the first experiment, 10 mg estradiol-17/β (E) was injected intramuscularly into all heifers. Seven heifers also received intramuscularly (im) 25 mg progesterone (P) at -12, 0, +12 and +24 hr relative to E injection. Estradiol had a biphasic effect on serum luteinizing hormone (LH) measured at various intervals. Serum LH was significantly (P<.01) depressed at 12 hr but preovulatory-like peaks of LH were noted between 20 and 32 hr after E. Neither the inhibitory feedback of E at 12 hr nor the stimulatory feedback at about 24 hr was significantly affected by P treatment. In the second experiment, 40 µg gonado-tropin-releasing hormone (GnRH) was injected im into all 13 heifers. Seven heifers also received 25 mg P at -28, -16 and -4 hr relative to GnRH. Peaks of serum LH were observed 1 to 3 hr post-injection in five of six heifers receiving only GnRH. Only three of seven heifers presented with P exhibited LH peaks after GnRH and their peaks tended to be smaller. Average serum LH for all heifers was decreased for at least 3 hr post-GnRH by progesterone pretreatment. In the third experiment, the conditions of experiment 2 were duplicated except that all heifers received E injections 16 hr before GnRH. In contrast to the results of experiment 2, P no longer decreased the GnRH-induced LH release. In conclusion, exogenous P did not antagonize the inhibitory nor the subsequent stimulatory feedback of injected E on LH release (experiment 1). Exogenous P did inhibit GnRH-induced release of LH in ovariectomized heifers in the absence of E (experiment 2) but not in the presence of exogenous E (experiment 3).

The catecholamine-containing tubero-infundibular system and the control of luteinizing hormone release in the rabbit

As determined by fluorescence histochemistry, the distribution of catecholamine-containing neurons in the hypothalamus of the female rabbit is similar to that seen in the rat. The fluorescence appearance of the hypothalamus was not appreciably different from normal at 0.25, 1, 4 or 24 h after mating, but in animals in which the synthesis of catecholamines was inhibited by the administration of the tyrosine hydroxylase inhibitor, H44/68, the number of fluorescent neurons seen in the nucleus periventricularis arcuatus following copulation was markedly reduced. However, the concentrations of luteinizing hormone (LH) in serum and in the pituitary glands of mated and unmated animals treated with H44/68 were not significantly different from those found in the corresponding control animals. This, together with the fact that ovulation followed mating in drug-treated rabbits suggest that a normal level of catecholamines in the tubero-infundibular system is not essential for the secretion of the amount of LH necessary for ovulation.