Gonadorelin Research Articles

Relationship between androgens, environmental factors and reproductive behavior in male white rhinoceros ( Ceratotherium simum simum)

We conducted a longitudinal study of the endocrine activity of free-range male white rhinos. An enzyme immunoassay to measure androgens in the feces was developed and validated to show that it can be used to study testicular activity. We identified two fecal metabolites similar to testosterone and dihydrotestosterone. Several lines of evidence suggest that these metabolites clearly reflect testicular activity. Firstly, the stimulation of testicular activity with synthetic GnRH caused a 156% increase in androgen metabolite concentrations in the feces 1 day after treatment. Secondly, androgen metabolite concentrations increased with sexual maturity in rhinos, and finally there was a correlation between testosterone concentrations in plasma and androgen metabolite concentrations in feces. Using the method that we developed, it was possible to establish whether a relationship exists between androgen metabolite concentrations, the behavior and environmental factors. Adult territorial males ( n = 5) had elevated androgen metabolite concentrations during months of high rainfall (September–February) compared to months of little or no rainfall (March–August). The increase in concentrations coincided with the beginning of the rainy season, suggesting a seasonal trend in reproduction. This trend was confirmed by behavior observations showing both a higher frequency of conceptions within the first 4 months of increased androgen metabolite concentrations, and a higher number of inter-sexual conflicts, reflecting the initial aggression between the sexes during the consort period. It was also evident that males accompanying a receptive female had higher fecal androgen metabolite concentrations compared to being alone. The elevated levels were likely induced by female presence.

Effects of a single injection of hCG or GnRH agonist on day 12 post mating on fetal growth and reproductive performance of sheep

Reproductive performance and fetal growth were determined when hCG (150 i.u. Pregnyl; n=44), GnRH (4 μg synthetic GnRH agonist, buserelin, Receptal; n=43) or saline (control, n=45) was administered (i.m.) to ewes on day 12 post mating during the breeding season. A total of 12 ewes was slaughtered on day 45 of pregnancy (four from each treatment group). Non-return rate and lambing rate were higher for ewes in the hCG (0.89 and 84%) and GnRH treated groups (0.86 and 79%) than for ewes in the control (0.69 and 62%) group ( P<0.05). The ewes in the hCG and GnRH groups also had more twins ( P<0.05). Birth weights of these twin lambs in the hCG and GnRH groups were heavier than those in the control group ( P<0.05), but this difference had disappeared at weaning 60 days later. Lamb mortality was similar among treatment groups resulting in a higher number of lambs weaned in the hCG and GnRH groups. The ovarian weights and the number of corpora lutea (CL) and luteal weights of ewes slaughtered on day 45 of pregnancy were greater ( P<0.05) in the hCG and GnRH treated groups than those measured in the control group. Administration of hCG on day 12 post mating increased gravid uterus weight, crown-rump-length (CRL), chorioallantois weight and total cotyledon weight ( P<0.05) of conceptuses recovered on day 45 of pregnancy compared to the control group. The weights of caruncules ( P<0.05) and placenta ( P<0.01) were higher in conceptuses of both the hCG and GnRH groups. The weights of fetuses in the hCG group were higher than those in both the GnRH and control groups ( P<0.05). In conclusion, both hCG and GnRH administration improved reproductive performance of ewes when administered on day 12 post mating. However, hCG and GnRH appeared to act differently on embryo survival because only hCG administration increased fetal growth.

GnRH agonist treatment on day 12 post-mating to improve reproductive performance in goats

Reproductive performance was determined in GnRH (4 μg synthetic GnRH agonist, buserelin, receptal; n=37) and saline (control, n=38) treated (i.m.) does on day 12 post-mating during the breeding season. Kidding rate was higher in the GnRH treated group (87%) compared to the control (68%) group ( P<0.05). The does in the GnRH group had more twins ( P<0.01) and consequently a higher total number of kids born and a larger litter size was recorded. Administration of GnRH on day 12 post-mating did not affect birth weight of kids. In conclusion, GnRH administration improved the reproductive performance of goats when administered on day 12 post-mating although the financial implications need to be evaluated.

Three Forms of Gonadotropin-Releasing Hormone, Including a Novel Form, in a Basal Salmonid, Coregonus clupeaformis1

Multiple forms of GnRH within individual brains may have different functions. However, some vertebrates such as salmonids continue to reproduce even though they have lost or do not express 1 of the 3 forms of GnRH found in most other teleosts. We examined a basal salmonid, lake whitefish, to determine the mechanism by which a reduction in the number of GnRH forms occurs. We identified for the first time 3 distinct GnRHs in a salmonid. One form is novel and is designated whitefish GnRH. The primary structure is pGlu-His-Trp-Ser-Tyr-Gly-Met-Asn-Pro-Gly-NH(2). HPLC and RIA were used for purification followed by Edman degradation for sequence determination. Mass spectroscopy was used to confirm the sequence and amidation of the peptide. The other 2 forms, salmon GnRH and chicken GnRH-II, are identical to the 2 forms found in salmon, which evolved later than whitefish. Synthetic whitefish GnRH is biologically active, as it increased mRNA expression of growth hormone and the alpha-subunit for LH and thyroid-stimulating hormone in dispersed fish pituitary cells. Our data support the hypothesis that the ancestral salmonid had a third GnRH form when the genome doubled (tetraploidization), but the third form was lost later in some salmonids due to chromosomal rearrangements. We suggest that the salmon GnRH form compensated for the loss of the third form.

Fetal growth and reproductive performance in ewes administered GnRH agonist on day 12 post-mating

Reproductive performance and fetal growth was determined in GnRH (4 μg synthetic GnRH agonist, Receptal) administered (i.m.) to ewes on day 12 post-mating ( n=103) compared to control ewes ( n=97) during the breeding season. Plasma progesterone and LH concentrations were analyzed. A total of 13 ewes was slaughtered on day 45 of pregnancy (six from control, seven from GnRH treated groups). GnRH administration on day 12 post-mating increased plasma progesterone concentration (4.39±0.25 ng/ml) compared to control group (3.43±0.15 ng/ml) on days 13–15 post-mating ( P<0.01). GnRH administration also increased plasma LH concentration between 1 and 4 h after GnRH administration ( P<0.01). Pregnancy rate was higher in GnRH treated group (84%) than control (66%) group ( P<0.05). The ewes in GnRH administered group had more twins ( P<0.05) than those in control group. The ovarian weights ( P<0.05) and the number of corpora lutea (CL) ( P<0.01) were greater in ewes slaughtered on day 45 of pregnancy in GnRH treated group than those in control group. GnRH administration on day 12 post-mating did not have any effect on products of conception at day 45 of pregnancy except on crown-rump length (CRL) of fetuses and cotyledon weight. CRL of fetuses and cotyledon weight in GnRH treated group was higher than those in control group ( P<0.05). In conclusion GnRH administration improved reproductive performance of ewes when administered on day 12 post-mating probably through its beneficial effect on embryo survival by enhancing luteal function, but not through stimulating fetal growth.

Pregnancy rates for Grade 2 embryos following administration of synthetic GnRH at the time of transfer in embryo-recipient cattle

To succeed with pregnancy a bovine embryo must overcome the luteolytic mechanism and achieve recognition of pregnancy. It is understood that well developed embryos are more successful in achieving recognition of pregnancy than poorly developed ones. Attempts have been made to assist this recognition of pregnancy by utilising a number of hormonal supplements with varying levels of success. A study was undertaken to test the hypothesis that supplementation with synthetic GnRH at the time of transfer of Grade 2 embryos will enhance pregnancy rates in recipients receiving this category of embryo. Pairs of fresh and frozen Grade 2 embryos ( n=38) from 34 donor animals were allocated to the trial. Thirty eight pairs of recipients were used and one of each pair was randomly assigned to receive treatment on the day of embryo transfer (Day 7) with 5 ml of gonadorelin, containing a synthetic gonadotrophin releasing hormone, 0.1 mg/ml. Pregnancy diagnosis was carried out from 42 days post-transfer by either palpation per rectum or ultrasound scanning. Treatment, embryo processing, side of transfer, parity of recipient, breed of recipient and breed of donor dam showed no statistically significant effect on pregnancy rate. The overall pregnancy rate in this study was within commercially accepted limits for Grade 2 embryos at 38.2%. The pregnancy rates were 34.2 and 42.1% for the GnRH-treated and control groups, respectively and were not significantly different at P<0.05. The failure of this treatment to improve pregnancy rates could be due to its effect being transitory therefore allowing subsequent pregnancy loss. The timing of the treatment post-transfer, treatment dose and potency of the GnRH analogue may also play a role in this. Further study is required to determine the hormonal or follicular status of prospective candidates for treatment before applying this as a whole herd regime.

Effect of acute administration of cocaine on pituitary gonadotrophin secretion in female rats

The aim of this study was to characterize the acute effects of cocaine administration on pituitary gonadotrophin secretion in adult female rats. Ovariectomized, oestradiol-treated rats were infused i.v. with 0.1 ml normal saline or 2 mg cocaine hydrochloride kg(-1). Blood samples were collected immediately before cocaine infusion and at 3, 10, 30 and 60 min after cocaine infusion. Circulating LH concentrations were increased by 10 min after cocaine administration (P < 0.05 versus saline-treated controls) and decreased thereafter. Serum FSH concentrations were not significantly different from those of saline-infused controls at any time. In a second experiment, oestradiol-treated, ovariectomized rats were infused i.v. with: saline only, 2 mg cocaine hydrochloride kg(-1) in saline, 200 ng synthetic GnRH in 100 microl PBS or 200 ng synthetic GnRH plus 2 mg cocaine hydrochloride kg(-1) in PBS. Blood samples were collected immediately before drug infusions and 20 min later. Cocaine had no effect on either GnRH-stimulated LH or FSH secretion. In a third experiment, pituitary cells were obtained from oestradiol-treated, ovariectomized rats. The cell cultures were exposed to 25 ng cocaine hydrochloride ml(-1), 10(-10)-10(-7) mol GnRH (-1) with and without 25 ng cocaine hydrochloride ml(-1), or vehicle only. Medium was collected before and after exposure to GnRH to determine concentrations of secreted LH and FSH. Similar to the results of the second study, cocaine had no effect on GnRH-stimulated LH or FSH secretion from pituitary cells in vitro. On the basis of these results it is suggested that acutely administered cocaine stimulates release of hypothalamic GnRH, which, in turn, stimulates pituitary gonadotrophin secretion. Acute administration of cocaine does not appear to affect pituitary gonadotrophin secretion directly.

Effect of acute administration of cocaine on pituitary gonadotrophin secretion in female rats

The aim of this study was to characterize the acute effects of cocaine administration on pituitary gonadotrophin secretion in adult female rats. Ovariectomized, oestradiol-treated rats were infused i.v. with 0.1 ml normal saline or 2 mg cocaine hydrochloride kg(-1). Blood samples were collected immediately before cocaine infusion and at 3, 10, 30 and 60 min after cocaine infusion. Circulating LH concentrations were increased by 10 min after cocaine administration (P < 0.05 versus saline-treated controls) and decreased thereafter. Serum FSH concentrations were not significantly different from those of saline-infused controls at any time. In a second experiment, oestradiol-treated, ovariectomized rats were infused i.v. with: saline only, 2 mg cocaine hydrochloride kg(-1) in saline, 200 ng synthetic GnRH in 100 microl PBS or 200 ng synthetic GnRH plus 2 mg cocaine hydrochloride kg(-1) in PBS. Blood samples were collected immediately before drug infusions and 20 min later. Cocaine had no effect on either GnRH-stimulated LH or FSH secretion. In a third experiment, pituitary cells were obtained from oestradiol-treated, ovariectomized rats. The cell cultures were exposed to 25 ng cocaine hydrochloride ml(-1), 10(-10)-10(-7) mol GnRH (-1) with and without 25 ng cocaine hydrochloride ml(-1), or vehicle only. Medium was collected before and after exposure to GnRH to determine concentrations of secreted LH and FSH. Similar to the results of the second study, cocaine had no effect on GnRH-stimulated LH or FSH secretion from pituitary cells in vitro. On the basis of these results it is suggested that acutely administered cocaine stimulates release of hypothalamic GnRH, which, in turn, stimulates pituitary gonadotrophin secretion. Acute administration of cocaine does not appear to affect pituitary gonadotrophin secretion directly.

The gonadotropin-releasing hormone family of neuropeptides in the brain of human, bovine and rat: identification of a third isoform

The mammalian gonadotropin-releasing hormone (GnRH-I), which regulates reproduction, was the first isoform of GnRH that was identified in mammals. Recently, we and others have demonstrated the existence of a second isoform of GnRH in the brain of mammals. The presence of a third isoform of GnRH, GnRH-III, in the brain of mammals is reported herein. GnRH-III, extracted from the brain of bovine and human, was purified by high performance liquid chromatography, using two distinct elution programs. In both, GnRH-III was eluted at the same positions as synthetic salmon GnRH, as demonstrated by radioimmunoassay. The luteinizing hormone-releasing activity of purified GnRH-III, using dispersed rat pituitary cells, was found to be similar to that of synthetic salmon GnRH. The total amount of GnRH-III, determined by radioimmunoassay, in the hypothalamus and midbrain of humans and calves is similar to that of GnRH-I. Immunohistochemical studies demonstrated GnRH-III-containing neurons in the hypothalamus and midbrain of human and GnRH-III fibers in the median eminence of rats. The distribution of GnRH-III in the brain suggests that in addition to a putative function as a neurohormone at the hypothalamic–pituitary axis, GnRH-III may have other functions. Our present results suggest that multiple isoforms of GnRH are present in the brain of mammals, and further studies are required in order to elucidate their biological functions.

Biological activity of the seminal plasma of alpacas: stimulus for the production of LH by pituitary cells.

South American camelids are induced ovulators and require a stimulus to trigger the LH surge responsible for the ovulation. Seminal plasma (SP) of fertile alpacas (Lama pacos) was tested using a bioassay of pituitary cells to study the effect of seminal plasma on LH release. Plates containing rat pituitary cells (2 x 10(5) cells/90-95% viability) were cultured adding: (A) whole SP (WSP) treated with charcoal-dextran, or 1:2 or 1:4 proportions diluted in culture medium (DMEM/HEPES + antibiotics), or (B) 1:2 SP + anti-GnRH rabbit serum (inhibitory potency 10(-5) M), or (C) 1:2 SP + anti-GnRH + 100 nM synthetic GnRH (buserelin acetate) or (D) 100 nM, 50 nM, 10 nM, and 1 nM synthetic GnRH. Concentration (ng/ml) of LH secreted (Sec) and contained (Con) was analyzed using RIA 125I and the percentage of Sec and Con in each experiment was determined. The results of LH Sec for the cells treated with 50, 10, and 1 nM GnRH were 39, 13, and 1.5%, respectively (r2 = 98.41%, r = 0.9920) but cells treated with 100 nM GnRH secreted 10% of LH. With WSP, 1:2, or 1:4 SP the LH Sec was of 44.5% (3.25 ng/ml), 27% (1.9 ng/ml), and 18% (1.2 ng/ml), respectively. The exposure of cells to 1:2 SP + anti-GnRH, or to 1:2 SP + anti-GnRH/100 nM GnRH produced 31% (2.20 ng/ml) and 30% (1.8 ng/ml) of LH Sec, respectively. These results suggest that the SP of alpacas could have some factor(s) different from GnRH that would contribute to the mechanisms of LH secretion and to the induced ovulation in the female alpaca.

Reproductive dysfunction in women with Albright's hereditary osteodystrophy.

Most individuals with Albright's hereditary osteodystrophy (AHO) have deficient expression or function of G(s alpha), the alpha subunit of the guanine nucleotide binding protein that stimulates adenylyl cyclase, and are resistant to parathyroid hormone (PTH) and other hormones that act via stimulation of adenylyl cyclase. To determine the incidence and etiology of ovarian dysfunction in women with AHO, we examined the reproductive history and hypothalamic-pituitary-ovarian axis in 17 affected women aged 17-43 yr. All patients had typical PTH resistance and an approximately 50% reduction in erythrocyte G(s alpha) activity, (0.43 +/- 0.03 vs. 0.92 +/- 0.08 for normal control subjects, P < 0.001). Fourteen of the 17 patients (76%) were oligomenorrheic or amenorrheic, more than half had delayed or incomplete sexual development, and only two had a history of earlier pregnancy. Most women were mildly hypoestrogenic, with normal to slightly elevated serum gonadotropin levels. Computer analysis of 24 hour LH measurement showed that the frequency of LH peaks/24 h in AHO women varied widely, but as a group they were not statistically different from a group of normal women studied in the early follicular phase. Administration of 100 microg synthetic GnRH produced normal FSH and LH responses. We conclude that reproductive dysfunction is common in women with AHO and probably represents partial resistance to gonadotropins.

Chicken GnRH II-like peptides and a GnRH receptor selective for chicken GnRH II in amphibian sympathetic ganglia.

Amphibia, like most vertebrate species, have two forms of GnRH, namely [Arg8]GnRH (mammalian GnRH) and [His5,Trp7,Tyr8] GnRH (chicken GnRH II). The differential distribution of the two peptides in the amphibian brain suggests that they may play different roles. Mammalian GnRH, which is found predominantly in the hypothalamus, is most likely the prime regulator of gonadotropin release, while chicken GnRH II, which occurs predominantly in the midbrain and hindbrain, may play a neuromodulatory role. In amphibian sympathetic ganglia, GnRH has been demonstrated to be a neurotransmitter where its release from the presynaptic nerve terminals reversibly inhibits M current, a time- and voltage-dependent potassium current. The occurrence of GnRH in sympathetic ganglia extracts from two amphibian species was investigated. Chicken GnRH II-like immunoreactivity was detected in extracts of bullfrog (Rana catesbeiana) and platanna (Xenopus laevis) sympathetic ganglia after high performance liquid chromatography. Under the chromatographic conditions used, a second unknown peptide co-eluted with synthetic mammalian GnRH, but showed no cross-reactivity with specific mammalian GnRH antisera. To test the possibility of the presence of a chicken GnRH II receptor in sympathetic ganglion neurones, competition binding of membranes extracted from the sympathetic ganglia of the two amphibian species was investigated with 125I-labelled GnRH agonists. The binding of 125-I-[His5,D-Arg6,Trp7,Tyr8]GnRH (a chicken GnRH II agonist) to membranes from the sympathetic ganglia of both amphibian species was specific and had a higher affinity than chicken GnRH II, mammalian GnRH and a mammalian GnRH agonist [D-Ala6,NMe-Leu7,Pro9-NHEt]GnRH. These findings suggest that endogenous chicken GnRH II may play a role in synaptic transmission in the sympathetic ganglia via a receptor specific for chicken GnRH II.

Hormone-Induced Ovulation of Sand Whiting SilIago ciliata

Sand whiting Sillago ciliata were captured by seine netting ocean beaches. Mature females were given single intraperitoneal injections of 300 IU•kg·1 human chorionic gonadotropin (hCG) or 0.5 ml•kg·1 Ovaprim (a synthetic GnRH analog with domperidone). One female and a spermiating male were then placed in 70-1 or 1,000-1 tanks. Both hCG and Ovaprim induced ovulation but not spawning in 38% and 75% of females, respectively (n=S). Females injected with distilled water (n=4) failed to ovulate. Fish were stripped, and the eggs fertilized 32-48 h after injection; mean fertilization was 85.6±15.4% (n=3, mean±SD) and 89.5±12.0% (n=6) in females injected with hCG or Ovaprim, respectively. Tank size had no apparent effect on the number of females that ovulated. A separate experiment was conducted to determine if natu­rally ovulating females could be successfully collected from the wild and stripped. The mean fertilization in naturally ovulating females was 71.0±17.1% (n=4), lower than for Ovaprim-in­jected mature fish colected at the same time (89.5±12.0%, n=2), but higher than in hCG-in­jected fish (32.7±5.5%, n=3). The fertility of eggs from females injected with hCG was higher in the first experiment. Reasons for the different response to hCG between experiments were un­clear, but the results suggest that Ovaprim is a more reliable hormone that hCG for inducing ovulation in sand whiting.

Alterations in hypophysial responsiveness to synthetic GnRH at different postpartum intervals in Murrah buffalo ( [formula omitted

The objective of this study was to investigate the hypophysial responsiveness to GnRH at different intervals post partum in Murrah buffalo. Plasma LH and FSH levels were measured at 1 h before and upto 6 h subsequent to the administration of GnRH (1 ug/kg body weight) or saline on Days 2, 20 and 35 post partum in 2 groups of buffalo (n=4 each). Plasma progesterone levels were measured in samples collected once daily from Day 3 to Day 46 post partum. Pretreatment basal LH levels exhibited a progressive increase from Day 2 through Day 35 post partum, while the basal FSH levels increased only until Day 20 post partum. Following a highly subdued LH response to GnRH on Day 2 post partum, a 408% increase (P < 0.01) was observed in the total LH released in response to GnRH on Day 20 post partum, followed by a 20% reduction (non-significant) over Days 20 to 35 post partum. The interval from parturition was highly correlated with total LH released (r = 0.711, P < 0.01). Unlike LH, a substantial amount of FSH was released following GnRH treatment on Day 2 post partum, which was not significantly different from the FSH response on Days 20 and 35 post partum. The LH and FSH response to GnRH was not significantly different between animals in which luteal activity resumed and in those which showed no luteal activity post partum. While pointing to a dramatic enhancement in the hypophysial responsiveness to GnRH between Days 2 and 20 post partum, these results suggest that pituitary responsiveness to GnRH does not appear to be the limiting factor for resumption of estrous cycles by Day 35 post partum in Murrah buffalo.

Choice of gonadorelin agonist for a given indication depends on the formulation

Choice of gonadorelin agonist for a given indication depends on the formulation

HUMAN PROSTATIC-CARCINOMA CELL-LINE LNCAP DEGRADES LUTEINIZING-HORMONE-RELEASING HORMONE

Recent evidence suggests a direct antiproliferative effect of LHRH agonists on the prostatic carcinoma cell line LNCaP. In the present study the possible presence of a LHRH degrading activity (LHRH-DA) in soluble fractions of LNCaP cell homogenates has been investigated. The results obtained show that an LHRH-DA is present in the soluble fraction of LNCaP cells with apparent Km and Vmax values of 31.6 mu M and 4.5 pmol/min/mu g protein respectively. The degradation pattern of LHRH is characterized by two major initial degradation products identified as LHRH 1-5 and LHRH 1-6 fragments. The degradation of the tracer [pGlu-H-3]LHRH, used as a substrate, is inhibited by synthetic unlabelled LHRH (IC50 7.9 mu M) and by several LHRH agonists with different kinetics and potencies; the LHRH agonist [DSer-(tBu)(6),Gly(10)-Aza]LHRH was the most potent blocker of LHRH-DA present in LNCaP cells; this enzymatic activity is also inhibited in a dose dependent manner by somatostatin, TRH, bacitracin and dithiothreitol. The LHRH-DA present in the soluble fraction of LNCaP cells does not seem to be modified by the deprivation of steroids from the culture medium, In conclusion, the presence in LNCaP cells of a soluble peptidase able to degrade LHRH might reinforce the possibility that the prostate is a target for the action of LHRH and of LHRH analogs.

The effects of long-acting oxytocin, GnRH and FSH administration on thyroxin, triiodothyronin, oestradiol 17-β and progesterone levels as well as conception rates in post-partum ewes

Abstract This work was a first attempt to discover whether the suppression of adenopituitary gonadotropin secretion might be responsible for a decrease of systemic T4 and T3 levels in the post-partum period in ewes, and also whether the depression of T4 and T3 levels might be retroactively responsible for a depression of sexual activity in the post-partum period and in spring. T4, T3, E2 and P4 levels were observed in four groups of ewes. After parturition (lambings took place in the first 10 days of February) the animals were treated with an oxytocin-based preparation (/2-0-methyltyrosin/deamino-1-carba-oxytocinum, Depotocin injection, Leciva), synthetic LH-RH (Dirigestran injection, Spofa) or pituitary gonadotropin FSH (Folicotropin injection, Spofa). Group 1 was the control group (n = 10), and each animal received 2 ml saline. The ewes in Group 2 (experimental; n = 9) were treated with 0.14 mg Depotocin per animal, the ewes in Group 3 (experimental; n = 10) were given 200 μg Dirigestran per animal, and the ewes in Group 4 (experimental; n = 5) received 160 IU Folicotropin. All preparations were administered in two doses: an intramuscular dose at 24 h post-partum and a subcutaneous dose at 72 h post-partum. On Day 51, oestrus was induced in all animals by combined Agelin (6-chloro-6-dehydro-16 methylene-17 α-hydroxyprogesterone) and PMSG treatment. Blood samples were obtained from the jugular vein at 24 h ante-partum (a.p.) (Day -1), at 36 h post-partum and on Days 4, 7, 14, 17, 21, 25, 34, 42 and 51 post-partum. When compared with the controls, altered T4 and T3 dynamics and significantly increased levels of T3 (between Days 4 and 25, P

Characteristics of alcoholics with the atypical aldehyde dehydrogenase 2 2 (ALDH2 2): A comparison of alcoholics about the genotypes of alcohol metabolizing enzymes

Consumption of alcohol, cocaine and opioids may induce changes in plasma reproductive hormone levels in both men and women. Since alterations in reproductive hormone homeostasis may affect behaviors associated with the expression of sexuality and aggression, the reinforcing properties of drugs and alcohol, for some persons, may be related to this process. There is also increasing evidence that the reinforcing properties of many abused substances may be due to the effects of these compounds on neuroendocrine control of sexual behavior and reproductive function. For example, persons who abuse alcohol and cocaine may do so in order to enhance both perception and expression of libidinal drive. The neuroendocrine concomitants of alcohol and drug reinforcement are determined by multiple factors. Enhancement or inhibition of gonadotropin secretion may affect target organ (gonadal-steroid) activity. Such modulation may co-vary with or, in part, determine the reinforcing properties of alcohol and drugs for libidinal behavior. Currently strategies exist for controlled laboratory studies of alcohol and drug effects on the hypothalamicpituitary-gonadal axis which incorporate social, expectancy and environmental factors which, in turn, may affect alcohol and drug reinforcement. Although precise modulation of expectancy or social factors in controlled neuroendocrine studies are difficult, it is possible to employ perturbation procedures in order to more precisely determine effects of drugs and alcohol on gonadal steroid hormones and behavioral reinforcement. For example, we can selectively perturbate the hypothalamic-pituitary-gonadal axis with exogenous compounds such as opiate antagonists, synthetic LHRH, hCG and dopamine itself since intravenous dopamine infusions cross the median eminence of the hypothalamus. These new experimental procedures are available for assessing the effects of drugs and alcohol on neuroendocrine systems which are no.ra l ly perturbated by endogenous peptide, glycoprotein and dopamine secretion. Application of these procedures may not only increase our knowledge about the causes of alcohol and drug abuse but also provide a rational basis for devising effective therapies for treating the adverse consequences of alcohol and drug abuse on reproductive function and behavior.

Nocturnal naloxone fails to reverse the suppressive effects of testosterone infusion on luteinizing hormone secretion in pubertal boys.

LH secretion is maximal during the night in pubertal boys, and testosterone (T) administration blunts this nocturnal rise of LH. We have previously shown that in pubertal boys, the acute negative feedback effects of T infusion on LH secretion during the daytime cannot be reversed by opioid receptor blockade. To determine whether the nocturnal secretion of LH in early puberty is regulated by endogenous opioid pathways, we determined whether naloxone during the night affected LH secretion or T-mediated suppression of LH secretion. Seven pubertal boys (bone age, 11-13.5 yr) were given a control infusion of saline, followed 1 week later by an infusion of T at 960 nmol/m2.h for 41 h starting at 2000 h. During both saline and T infusions, six iv boluses of saline were given hourly beginning at 2400 h on the first day, and six iv boluses of naloxone (0.1 mg/kg each) were given hourly beginning at 2400 h on the second day. Starting at 2200 h, blood was obtained every 15 min for LH and every 30 min for T determinations for 14 h each night. Pituitary responsiveness was assessed at the end of each study night by i.v. bolus administration of 250 ng/kg synthetic GnRH. T infusion increased the mean T concentration 6-fold (P < 0.0001) and suppressed the mean plasma LH concentrations from 5.6 +/- 0.6 to 3.8 +/- 0.6 IU/L (P < 0.01). The nocturnal augmentation of LH secretion was suppressed by the infusion of T, and this suppression was not reversed by naloxone. The mean nighttime plasma LH (2400-0600 h) was 8.1 +/- 1.1 IU/L during the control saline infusion and 5.1 +/- 0.6 IU/L during the T infusion (P < 0.01). The mean LH level was 4.0 +/- 0.7 IU/L during the administration of naloxone boluses concomitantly with the T infusion, not significantly different from that during the T infusion. Likewise, LH pulse frequency during the same time period was decreased by T infusion from 0.6 +/- 0.1 to 0.36 +/- 0.04 pulses/boy.h (P < 0.05), and it was unaltered by coadministration of naloxone (0.38 +/- 0.12 pulses/boy.h). Naloxone administration during the saline infusion did not increase either the mean plasma LH concentration (7.5 +/- 0.7 IU/L; P = NS vs. saline control) or the LH pulse frequency (0.69 +/- 0.1 pulses/boy.h; P = NS vs. saline control). Pituitary responsiveness to GnRH was similar on each of the 4 nights during either saline or T infusions.(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of synthetic GnRH analogues and dopamine antagonists on the maturation of Pacific mullet, Mugil so-iuy Bas.

. The effect of two GnRH-As – des Gly10 (D-Ala)6 LHRH and des Gly10 (D-Tle)6 GnRH in total doses 10–249mu;g/kg – and four neuroleptics – pimozide, sulpiride, metoclopramide and isofloxythepin in total doses 1–50mg/kg - and environmental temperatures on the development of final stages of Pacific mullet oogenesis was investigated. The best technique of those used by us for spawning stimulation of Pacific mullet, Mugil so-iuy Bas., females is shown to be administration of neuroleptics in doses of l-8mg/kg with posterior injections on GnRH-A in doses of 25 and 50mu; g/kg applied 4 and 28h respectively after the neuroleptic injection. At water temperatures below 17°C, ovulation does not occur unless the optimal stimulation is applied.