Plasma 17β-estradiol Levels Research Articles

Expression of estrogen receptor α and β genes in the mediobasal hypothalamus, pituitary and ovary during the canine estrous cycle

Estrogen receptor α (ERα) and ERβ mRNA levels were measured in the mediobasal hypothalamus, the anterior pituitary and the ovary of beagle bitches at various stages of the estrous cycle. With polymerase chain reaction analysis we detected ERβ gene transcripts in all tissue samples. The levels of hypothalamic and pituitary ERα and β mRNAs increased from mid anestrus to proestrus and declined thereafter. In the ovary, ERα mRNA levels increased from proestrus to diestrus and were positively correlated with plasma progesterone levels ( r=0.62, P<0.01), whereas ERβ mRNA levels increased from mid anestrus to proestrus and were positively correlated with plasma estradiol-17β levels ( r=0.73, P<0.001). These results suggest that the rise in hypothalamic and pituitary ERα and β mRNAs is associated with termination of anestrus, and that increases in ovarian ERα and β mRNAs may be involved in initiating development of the follicle or corpora lutea.

Neurocognitive functioning in subjects with eating disorders: the influence of neuroactive steroids

Background Neuropsychological studies in subjects with eating disorders (EDs) have reported conflicting findings, which might be accounted for by several confounding variables, including neuroendocrine changes. Methods General abilities, executive functions, attention, and noneffortful learning were assessed in 45 patients with EDs and 45 healthy comparison subjects (HCS). Plasma levels of 17β-estradiol, cortisol, allopregnanolone, dehydroepiandrosterone and its sulfate metabolite (DHEA and DHEAS) were evaluated in a subsample of patients and HCS. The influence of clinical, demographic, and neuroendocrine variables on neurocognitive performance was explored. Results Patients were slower than HCS on noneffortful learning and more accurate on a spatial executive task. DHEA and DHEAS were increased and positively correlated with accuracy on the executive task, while cortisol positively correlated with speed of noneffortful learning. Conclusions A subtle impairment of noneffortful learning is the only neuropsychological deficit in patients with EDs. Changes in neuroactive steroids influence neurocognitive performance.

Influence of the menstrual cycle on the timing of acute coronary events in premenopausal women

During their reproductive years, women have a low incidence of coronary artery disease (1,2), which increases markedly 10 to 15 years after menopause (3). It has long been hypothesized that this increased risk is at least in part due to the absence of female hormones, in particular, 17 -estradiol (4). This hypothesis was supported by data from epidemiological studies, which suggested that hormone replacement therapy would protect postmenopausal women from coronary artery disease (5– 8). However, recent placebo-controlled trials designed to test the cardioprotective effects of a regimen of estrogens plus progestin have found no reduction in cardiovascular events or progression of angiographic lesions (9 –12). Nevertheless, acute administration of 17 -estradiol affects the vasculature by modulating the nitric oxide–Larginine pathway (13,14), and improves endothelial function (15) and prolongs the time to ST-segment depression and exercise time, in postmenopausal women with coronary artery disease (16). These data suggest that the acute effects of 17 -estradiol could subside rapidly when levels are low during menses. Therefore, we sought to determine whether premenopausal women would be at greater risk of developing an acute coronary event when blood levels of 17 -estradiol levels are low during the menstrual cycle.

Evidence that temperature change cues reproductive development in the spiny damselfish, Acanthochromis polyacanthus

The role of temperature in the reproductive development of the spiny damselfish, Acanthochromis polyacanthus, was assessed by measuring changes in ovulatory periodicity and plasma levels of gonadal steroids in response to temperature shifts of 4°C. This was assessed in sexually mature, paired and unpaired fish. The effect of brood presence on reproductive activity was also assessed. Temperature change but not brood presence significantly affected the spawning periodicity of sexually mature, reproductively active pairs. A temperature increase from 24°C to 28°C resulted in a decrease in the ovulatory period from 32 days to 21 days. Incubation temperature was found to dramatically affect survival of the egg clutches with only one of 13 egg clutches surviving to hatching at 24°C, compared with 50 of 51 egg clutches surviving at 28°C. Gonadal steroid production was positively correlated with temperature increase in paired fish. Plasma levels of 17β-estradiol and testosterone (T), increased significantly in female fish, whereas there was no change in T and 11-ketotestosterone, in paired male fish exposed to a temperature increase from 24°C to 28°C. In unpaired fish, temperature change had ambiguous affects on plasma steroid levels, suggesting that social context is necessary for stimulation of reproductive development by temperature.

Estrogen effect on some enzymes of female rats after downhill running.

The study investigates the effect of administered estrogen on plasma creatine kinase (CK) and lactate dehydrogenase (LD) levels in female ovariectomized rats after downhill running. Rats ovariectomized before sexual maturity were subcutaneously implanted with pellets containing 17β-estradiol or placebo. Three weeks later they were subjected to a 90-min intermittent downhill running protocol. Blood samples were obtained from the jugular vein immediately after and 72 h after exercise for determination of plasma CK, LD and 17β-estradiol levels. A two-way analysis of variance was used for data evaluation. Plasma CK and LD levels were significantly lower (p&lt;0.05) in the estrogen-supplemented, ovariectomized animals which suggests that less muscle damage occurred compared to the controls immediately and 72 h after exercise. Estrogens may have a protective effect on muscle tissue possibly due to their antioxidant and membrane stabilizing properties.

Enhancement of aromatase gene expression in the mediobasal hypothalamus during anestrus in the beagle bitch

The relationships among expression of cytochrome P450 aromatase (P450arom) mRNA in the mediobasal hypothalamus (MBH), ovarian aromatase activity, and estrogen secretion were examined throughout the estrous cycle in beagle bitches. Using polymerase chain reaction (PCR) analysis we were able to detect P450arom gene transcripts in the canine MBH. The level of hypothalamic P450arom mRNA increased during the progression of anestrus and declined thereafter. Ovarian P450arom activity, as measured by a 3H 2O assay, were low in anestrus, increased in proestrus, and declined thereafter. Ovarian P450arom activity and plasma estradiol-17β levels were positively correlated ( r=0.77, P<0.05). These results suggest that enhancement of hypothalamic P450arom gene expression is associated with termination of anestrus.

Capture and handling stress affects the endocrine and ovulatory response to exogenous hormone treatment in snapper, Pagrus auratus (Bloch &amp; Schneider)

Sexually mature female hatchery-reared snapper, Pagrus auratus (Bloch & Schneider) were captured from sea cages by handline and injected at first capture (control) or 24 h after capture, transport and subsequent confinement (delayed injection) with either saline, luteinizing hormone releasing hormone analogue, human chorionic gonadotropin, or 17α-hydroxyprogesterone. Blood was sampled before hormone treatment and again after 168 h, and fish were checked daily for ovulation. Plasma levels of 17β-estradiol (E2), testosterone (T), 17α, 20β dihydroxy-4-pregnen-3-one (17, 20βP) and cortisol were determined by radioimmunoassay. The ovulatory response was assessed from the proportion of fish ovulating, ovulation volume, egg quality and fertility. A delay in injection resulted in significantly lower plasma E2 and T levels in response to hormone treatment, smaller ovulation volumes, and poorer egg quality than in control fish. The results are consistent with the generally inhibitory effects of stress on reproduction in fish, and confirm the requirement to treat fish with hormones designed to induce ovulation, as soon as possible after capture and disturbance.

Estrogen increases endothelial nitric oxide synthase via estrogen receptors in rat cerebral blood vessels: effect preserved after concurrent treatment with medroxyprogesterone acetate or progesterone.

In vivo and in vitro rat models of hormone therapy were used to test the following hypotheses: (1) estrogen acts directly on cerebrovascular estrogen receptors to increase endothelial nitric oxide synthase (eNOS); (2) increased protein correlates with higher NOS activity; and (3) effects of estrogen on eNOS are altered by concurrent treatment with either medroxyprogesterone acetate (MPA) or progesterone. Blood vessels were isolated from brains of ovariectomized female rats; some were treated for 1 month with estrogen, estrogen and progesterone, or estrogen and MPA. Isolated cerebral vessels were also treated in vitro with estrogen in the absence and presence of progesterone, MPA, tamoxifen, and the estrogen receptor antagonist ICI 182 780. Levels of eNOS were measured by Western blot, and NOS activity was measured by [14C]arginine-[14C]citrulline conversion. Chronic hormone treatment in vivo resulted in plasma levels of 17beta-estradiol, progesterone, and MPA in the range of values found in humans. Estrogen treatment resulted in higher levels of cerebrovascular NOS activity that paralleled increases in eNOS protein. In vitro estrogen treatment for 18 hours also resulted in a concentration-dependent increase in eNOS protein (EC50 approximately 300 pmol/L) that was completely prevented by estrogen receptor antagonists tamoxifen or ICI 182 780. However, cotreatment with progesterone or MPA, either in vivo or in vitro, did not alter the effect of estrogen on eNOS protein. Estrogen receptor activation in cerebrovascular tissue results in increased eNOS activity and protein levels. The latter effect persists in the presence of either progesterone or MPA. Thus, increased NO production by eNOS may contribute to the neuroprotective effects of estrogen.

Tetrahydrobiopterin Improves Vascular Endothelial Function in Ovariectomized Rats

The goal of the present study is to investigate the role of tetrahydrobiopterin (BH₄) in the vascular response in ovariectomized rats. Rats were randomly assigned to two groups: (1) sham group: sham-operated female rats, and (2) Ovx group: rats were ovariectomized. Our results have shown that the plasma 17β-estradiol levels in the Ovx group at the end of the experiment were significantly lower than in the sham group. Vasoreactivity assessed with intact aortic rings indicated that the phenylephrine-induced vasocontractile response to aortic rings from the Ovx group was greater than that of the sham group. In contrast, the vasodilator responses to acetylcholine and L-arginine (L-Arg) in the sham group were significantly greater than in the Ovx group. Differences in vasoreactivity in denuded aorta between the two groups were not noted. Moreover, exogenous BH₄ significantly restored L-Arg-induced vasodilator responses in the Ovx group. However, this improvement effect was not found in the sham group. In addition, there were significant increases in superoxide anion production in aortic tissue and significant decreases in plasma nitric oxide levels in the Ovx group. Furthermore, BH₄ contents in the aorta in the Ovx group were significantly decreased compared with the sham group. In conclusion, the present study demonstrates that the impairment of vascular reactivity was found in the ovariectomized rats. The possible mechanism of this defect may have resulted from the deficiency of available BH₄. Thus, this study may provide a novel therapeutic strategy for the treatment of postmenopausal cardiovascular disorders.

Endogenous origin of norandrosterone in female urine: indirect evidence for the production of 19-norsteroids as by-products in the conversion from androgen to estrogen

Recently the use of high resolution mass spectrometry or tandem mass spectrometry has enabled the detection of low amounts of anabolic steroids. As a consequence, the post-administration detection time of these drugs has been extended. Recent investigations have shown that norandrosterone, previously unequivocally regarded as evidence of nandrolone administration, might be an endogenous steroid present in small amounts in urine of humans. In this study, very low concentrations (<1 ng/ml) of norandrosterone in urine of a female athlete were detected using tandem mass spectrometry. The presence of norandrosterone was strongly correlated with high plasma 17β-estradiol levels during the menstrual cycle. Analysis of urine samples from pregnant women supports the hypothesis of formation of precursors for urinary 19-norandrosterone during aromatization of androgens to estrogens. The detection of low urinary concentrations of norandrosterone (0.2–0.5 ng/ml) in samples after strenuous exercise could be regarded as an additional evidence for the existence of such a pathway.

Characterization of late-pregnant rat uterine contraction via the contractility ratio in vitro Significance of α 1-adrenoceptors

The aim of this study was to characterize the ability of late-pregnant (days 15–22) rat uterine tissue rings to contract in response to electric field stimulation in vitro. For this purpose, maximum rhythmic contractions were elicited by optimum choice of the period time and the pulse width, the two main parameters of electric field stimulation. In parallel, the plasma 17β-estradiol and progesterone levels were determined. It was found that the contractility ratio, i.e. the quotient of the optimum pulse width and the period time, is a good parameter with which to express the contractility. The larger the contractility ratio, the better the ability to contract. Evaluation of the area under the curve did not furnish information relating to the contractility in this method. A very close correlation was observed between the contractility ratio and the quotient of the 17β-estradiol and progesterone levels on different days, demonstrating that the in vitro ability characterized by the contractility ratio is in keeping with the physiological regularity. There was also a very close correlation between the contractility ratio and the quotient of the α 1- and β-adrenergic receptors, suggesting the main role of the numbers of α 1-receptor in pregnant uterine contractility. It is believed that this is the first in vitro model to give a numerical measure concerning the ontogeny of uterine contractility in late pregnancy.

Plasma steroid levels in female flounder ( Platichthys flesus) after chronic dietary exposure to single polycyclic aromatic hydrocarbons

The chronic effects of polycyclic aromatic hydrocarbons (PAHs) on ovary development, total hepatic lipids and plasma sex- and corticosteroid levels in female flounder ( Platichthys flesus) were examined. Sexually mature feral female flounder were exposed via the diet to phenanthrene (0.5, 2.5 or 12.5 nmol/g food) or chrysene (0.4 nmol/g food) for 12 weeks, during the previtellogenic phase of the annual reproductive cycle. PAH exposure did not directly affect germ cell development since no structural and/or developmental differences were observed between control and exposed fish. On the contrary, all treatments resulted in altered plasma steroid levels. The most pronounced effect was the significant decrease in plasma 17β-estradiol to 19±11%, 27±7%, 63±20% and 61±12% in relation to control fish, respectively, in flounders exposed to 12.5, 2.5 or 0.5 nmol phenanthrene/g food and 0.4 nmol chrysene/g food. Impaired ovarian growth was not observed, most likely because experiments were ended before the period of vitellogenesis, even though a non-significant general decline in total hepatic lipids could be observed. Moreover, all exposed flounders, except fish fed with the highest amount of phenanthrene, showed a negative correlation between plasma 17β-estradiol and 17α-hydroxyprogesterone levels ( r=−0.46). One possible explanation is that PAH action may be mediated by a specific inhibition of steroidogenic enzymes. These findings provide evidence that selected PAHs are antiestrogenic xenobiotics with the capability to impair female teleost reproductive function.

Oviductal isthmic motility in relation to ovulation and endocrine changes in unrestrained sows

This study was designed to characterize changes in the motility of the oviductal isthmus in relation to endocrine changes around ovulation in unrestrained sows in their normal environment. Oviductal isthmic motility was monitored on Poly view ™ from 11 h prior to and up to 36 h after ovulation in 13 unrestrained multiparous sows during their second estrus after weaning, using a pressure microtransducer implanted 3 cm into the isthmus. Both the maximum, minimum and mean pressures and the frequency of phasic pressure fluctuations were high prior to ovulation but declined significantly (P<0.05) at 9 to 12 h, 13 to 16 h, 13 to 16 h and 5 to 8 h after ovulation, respectively. Plasma estradiol-17β and prostaglandin F 2α metabolite levels declined significantly (P<0.05) at 4 to 7 h prior to ovulation while progesterone levels increased significantly (P<0.01) at 5 to 8 h after ovulation. The decrease in the plasma estradiol-17β levels was correlated to the decrease in maximum and mean pressures and the frequency of phasic pressure fluctuations (n=113; r=0.30, 0.25, 0.25, respectively; P<0.01) but not to the decrease in minimum pressure (n=l 13; r=0.17, P>0.05). Similarly, the decrease in PGF 2α metabolite levels was correlated to the decrease in minimum, maximum and mean pressures and the frequency of phasic pressure fluctuations (n=112; r=0.43, 0.35, 0.38, 0.32, respectively; P<0.001). Conversely, the increase in plasma progesterone levels was correlated to the decrease in minimum, maximum and mean pressures and the frequency of phasic pressure fluctuations (n=113; r=−0.56, −0.70, −0.68, −0.60, respectively; P<.0001). Therefore, the pressure parameters seem to be influenced by changes in the levels of estradiol-17β, prostaglandin F 2α and progesterone with respect to ovulation.

Partial or total replacement of fish meal byplant protein affects gonadal development and plasma17 β-estradiol levels in female Nile tilapia

This study was conducted to evaluate theeffect of plant protein‐based diets on gonadaldevelopment and plasma 17 β-estradiol (E2) levelin female Nile tilapia Oreochromis niloticus.Fish with a mean body weight of 6.7 (0.1) g were fedfour different diets with the same digestible protein(DP) and digestible energy (DE) containing gradedlevels of a mixture of plant ingredients as partial ortotal replacement of fish meal protein for 20 weeks.The control diet (D0) was based on fish meal, twodiets containing 33% (D33) and 66% (D66) of plantprotein, and one diet containing only plant protein(D100). Fish were sampled at 12 and 20 weeks. Nosignificant differences were found in different stagesof oocyte development and plasma E2 levels betweentilapia fed diets D0 and D100 at 12 weeks. Eight weekslater tilapia fed diet D0 showed a higher (P < 0.05)level of E2 than the D100 group. This difference andthe reduced proportion of vitellogenic and matureoocytes demonstrated that diets containing only plantprotein are less efficient in terms of tilapia growthand consequently ovarian development.

Dual effect of female sex steroids on drug-induced gastroduodenal ulcers in the rat

Since the sexual dimorphism of gastroduodenal ulcers is well known and might possibly relate to the actions of sex hormones, we studied the role of the female sex steroids, progesterone and 17β-estradiol in cysteamine-induced mucosal ulcers in female Wistar rats (200–220 g). Administration of cysteamine (400 mg/kg, s.c.) provoked macroscopic gastroduodenal mucosa injury as assessed planimetrically, an increase in microvascular permeability in the stomach and the duodenum as assessed by extravasation of radiolabelled albumin and decreased gastroduodenal mucus levels as assessed by the Alcian blue technique. Ovariectomy (2 weeks before cysteamine) decreased plasma 17β-estradiol level as assessed by radioimmunoassay, gastroduodenal macroscopic injury and albumin extravasation and increased mucus levels following cysteamine challenge. Administration of progesterone (10–50 mg/kg/week, s.c.) attenuated in a dose-dependent manner cysteamine-induced gastroduodenal mucosa injury and microvascular leakage, while it increased mucus levels in the stomach and the duodenum. In contrast, administration of 17β-estradiol (1–5 mg/kg/week, s.c.) dose-dependently augmented gastric and duodenal macroscopic mucosa lesions and microvascular injury provoked by cysteamine and caused a further reduction in gastroduodenal mucus levels observed after cysteamine administration. In different experiments, ovariectomy decreased indomethacin-induced gastroduodenal injury. The injection of 17β-estradiol (1–5 mg/kg/week) did not affect gastroduodenal damage, while treatment with progesterone (10–50 mg/kg/week) protected against indomethacin-provoked mucosa ulcers. It is concluded that female sex steroids play a role in drug-induced gastroduodenal ulcers by modulating microvascular permeability and mucus secretion.

Effects of the Aromatase Inhibitor Fadrozole on Plasma Sex Steroid Secretion and Ovulation Rate in Female Coho Salmon,Oncorhynchus kisutch,Close to Final Maturation

Plasma levels of 17β-estradiol, 17α,20β-dihydroxy-4-pregnen-3-one (17α,20β-P), and testosterone were measured in adult female coho salmon in late vitellogenesis, approximately 1.5 months before spawning and just before and following intraperitoneal injection with the aromatase inhibitor (AI) Fadrozole. Injection at dosages of 0.1, 1.0, and 10.0 mg AI/kg body wt caused a significant drop in plasma 17β-estradiol levels relative to preinjection values within 3 or 6 h. Injection of 10 mg AI/kg body wt caused a significant increase in plasma 17α-20β-P levels within 3 h. Ten days after injection 67% of the fish treated with 10 mg AI/kg body wt had ovulated in contrast with 0% in the group injected with 0.1 mg AI/kg body wt. The fertilization rate of the eggs varied between 96% in the control group and 85% in the groups injected with AI. We conclude that the shift from 17β-estradiol to 17α,20β-P biosynthesis, which is characteristic of maturingOncorhynchussp., was advanced significantly by treatment with AI and that Fadrozole can be used as a tool to investigate periovulatory endocrine changes in salmon.

Effects of the aromatase inhibitor Fadrozole on plasma sex steroid secretion and oocyte maturation in female coho salmon (Oncorhynchus kisutch) during vitellogenesis

17β-estradiol, 17α-20β-dihydroxy-4-pregnen-3-one (17α-20β-P), and testosterone levels were measured in plasma samples obtained from vitellogenic coho salmon (Oncorhynchus kisutch) before and 32 days after injection of the aromatase inhibitor Fadrozole (AI). Plasma 17β-estradiol levels decreased significantly 6 h after injection in all AI treated fish. The higher the dose the longer the maintenance of low plasma 17β-estradiol levels. Inversely, plasma 17α-20β-P increased significantly 6 h after injection in all AI treated fish, and the higher the dose the longer the maintenance of high plasma 17α-20β-P levels. At 48 h after injection plasma testosterone levels were significantly higher in the AI treated groups. The oocyte maturation index showed that multiple injections with AI retarded oocyte development. Besides, oocyte diameter and GSI were lower in the same group, which presented high incidence of atresia of vitellogenic oocytes. The ovarian follicles and brain of the fish which received multiple injections secreted less 17β-estradiol, in vitro. These findings suggest that aromatase inhibitors such as Fadrozole may have a potential as a tool to regulate sexual development in salmon.

Effect of protein source on the reproductive performance of female rainbow trout, Oncorhynchus mykiss (Walbaum)

Two-year-old rainbow trout, Oncorhynchus mykiss (Walbaum), females were fed three different diets containing animal protein R1 or vegetable protein R2 and R3 over 12 months from March 1993 until February 1994. Diets containing vegetable protein slightly depressed broodstock growth rates, although the final weight differences among groups were not statistically significant. The mean total fecundity (eggs female -1 ) was significantly higher (P<0.05) in group R1. With regard egg composition, amino acids levels in group R3 were significantly lower (P<0.05) than in the other groups. Although the total amino acids of eggs from the R1 and R2 groups presented a similar pattern, the essential amino acids lysine, threonine, cystine and isoleucine were lower in the R2 group. The ω6 and ω3 fatty acid levels of the eggs were also affected by the protein source of the diet. In both the R2 and R3 groups, the plasma levels of 17β-estradiol reached a maximum level one month later than the R1 group. For the R2 and R3 groups, plasma levels of vitellogenin peaked after a one-month delay; peak values were significantly lower (P<0.05) than in the R1 group. Similarly, the vitellogenin content of the eggs was in accordance with plasma levels in broodstock females. The results of the present study demonstrated that the composition of diet significantly affected reproductive indices and composition of the eggs.

Methallibure-induced inhibition of hypothalamo-hypophyseal-ovarian activity in the catfish Heteropneustes fossilis involves changes in hypothalamic monoamine activity

Administration of Methallibure, a non-steroidal gonadotropin (GTH) inhibitor 20 μg g−1 body weight; i.p., daily for 10 days, to prespawning phase female Heteropneustes fossilis inhibited the brain-pituitary-ovarian axis as indicated by significant reductions in plasma and pituitary levels of GTH-II, and plasma levels of 17β-estradiol (E2) and testosterone. Concurrently, the treatment resulted in significant reductions in the hypothalamic content of serotonin, noradrenaline (and adrenaline) that stimulate, and a significant elevation of dopamine that inhibits GTH-II release in this species. Activities of the monoamine degrading enzymes, monoamine oxidase and catechol-O-methyltransferase were significantly increased, while that of the synthesizing enzymes, dopamine-β-hydroxylase and phenylethanolamine-N-methyltransferase were significantly decreased. These results suggest that the mechanism of inhibition of GTH-II secretion includes, among others, differential actions of the drug on hypothalamic monoamine metabolism.

The influence of reproductive status on the stimulatory action of N-methyl-D,L-aspartate on growth hormone secretion, in vitro in rainbow trout, Oncorhynchus mykiss

The glutamate agonist, N-methyl-D,L-aspartate (NMA) stimulates the secretion of growth hormone (GH) from pituitary fragments in vitro and increases plasma GH levels in vivo in rainbow trout, Oncorhynchus mykiss (Flett et al. 1994; Holloway and Leatherland 1997a,b); however gonadal steroid hormones appear to modulate this response in experimental situations. This study examines whether steroid hormones also modulate the GH-regulatory actions of NMA during the normal reproductive cycle of rainbow trout by examining the relationship between the stage of sexual maturation and the pituitary release of GH in vitro in response to an NMA (10-8 M) challenge. NMA had no effect on mean GH release from the pituitary glands of fish that were immature (GSI <1.0), from males during early development (GSI 1.0-3.0), or from sexually mature males (with free running milt) and females (ovulated). However, NMA significantly increased GH release from pituitary glands taken from females during the early stages of gonadal growth (GSI 1.0-9.0) and from males and females sampled during the later stages of gonadal growth (males GSI 3.01-6.0; females GSI 9.01-15.0). The GH-stimulatory action of NMA in males and females progressed to a maximum effect during the late stages of gonadal growth, and disappeared in ovulated females and free running males. Moreover, in female fish, the maximal GH release in response to the NMA challenge is positively correlated with plasma 17β-estradiol levels; no such correlation was evident for plasma testosterone levels in males. Changes in the GH response to NMA during maturation while gonadal steroid levels fluctuate provides further evidence to suggest that the effects of NMA on GH secretion are intimately linked to endogenous gonadal steroid hormone levels.