The Posttraumatic Growth Inventory: an examination of the factor structure and invariance among breast cancer survivors.

OBJECTIVE: The present study tested the proposed five-factor structure and invariance of the Posttraumatic Growth Inventory (PTGI; Tedeschi & Calhoun, 1996) in a sample of physically active breast cancer survivors. METHODS: A sample of breast cancer survivors (N=470, Mage=57.3, SD=7.8 years) completed the PTGI and a demographic questionnaire. The factor structure, factorial invariance, and latent mean invariance were tested using maximum likelihood structural equation modeling. RESULTS: Preliminary analyses showed acceptable reliability for the PTGI subscales (alpha<0.83). Confirmatory factor analysis (CFA) supported the five related factors corresponding to: relating to others, new possibilities, personal strength, spiritual change, and appreciation of life (chi(2) (179)=822.53, CFI=0.97, NNFI=0.96, SRMR=0.05, RMSEA=0.09). Multigroup CFA supported the invariance of the PTGI across age groups, treatment type, time since diagnosis, and time since last treatment. CONCLUSIONS: These findings provide support for (1) the multidimensional nature and factorial validity of the PTGI, and (2) the use of the PTGI in future research examining posttraumatic growth within samples of physically active breast cancer survivors.

Characterization of two forms of cocaine- and amphetamine-regulated transcript (CART) peptide precursors in goldfish: molecular cloning and distribution, modulation of expression by nutritional status, and interactions with leptin.

Complementary DNAs encoding two forms of cocaine- and amphetamine-regulated transcript (CART) peptide precursors were identified from goldfish brain and named CART I and CART II. Each cDNA contains a signal peptide sequence, the putative CART-like peptide, and a carboxy-terminal extension peptide. Form I encodes a 117-amino acid pro-CART, whereas form II encodes a 120-amino acid pro-CART. Both forms resemble mammalian CART peptides. Each goldfish CART precursor is encoded by three exons interrupted by two introns within genomic DNA. RT-PCR, slot blot, and Northern blot analysis showed that the mRNAs for form I and II precursors have a widespread distribution. Form I and II are present in the brain, pituitary, eye, gonads, and kidney. Form I is also present in the gill. In the brain, form I is predominant in the olfactory bulb and hypothalamus, and form II is predominant in the optic tectum. Food deprivation for 96 h induced a decrease in form I mRNA levels in the telencephalon-preoptic region, hypothalamus, and olfactory bulb and in form II mRNA expression in the olfactory bulb. An increase in mRNA levels was observed 2 h following a meal in the olfactory bulbs and hypothalamus for form I whereas no postprandial changes in form II mRNA levels were observed. Intracerebroventricular injections of human CART alone induced a significant decrease in food intake. Injections of leptin reinforced the inhibition of feeding behavior and food intake seen in CART-treated fish. Central injection of leptin induced an increase in CART I mRNA in the optic tectum, hypothalamus, and olfactory bulbs but had no effect on CART II mRNA expression in the brain. These results suggest that CART peptides act as leptin-regulated satiety factors in goldfish and that they might have other physiological roles besides feeding, possibly in sensory information processing.

Neuropeptide Y stimulates food consumption through multiple receptors in goldfish.

In this study, the acute effects of brain intracerebroventricular (icv) injections of mammalian neuropeptide Y (NPY) Y1 ([31Leu,34Pro]NPY), Y2 (NPY2-36) and Y5 ([D-32Trp]NPY) receptor subtype agonists on food intake in goldfish were examined. Icv injection of Y1 and Y5 receptor agonists in dosages of 1 and 5 ng/g exhibited dose-dependent effects on food intake; however, higher dosages of both receptor subtypes had desensitising effects on food intake, and caused a decrease in food intake in comparison to the lower dosages. At 10 and 20 ng/g, Y1 receptor agonist-treated fish exhibited feeding significantly lower than intact and saline-injected fish; fish treated with the same dosages of Y5 agonist exhibited food intake similar to intact and saline-injected fish. Y2 agonist had no effects on food intake. Co-icv administration of Y1 and Y5 agonists in dosages of 1 and 5 ng/g caused enhanced food intake that was additive of the individual doses alone. However, desensitising one receptor did not influence the responsiveness of the other. Co-icv injection of Y1 receptor agonist in desensitizing high dosages (10 and 15 ng/g) with Y5 receptor agonist in lower doses (1 and 5 ng/g, respectively) or vice versa, resulted in a food intake similar to the dosages of Y1 and Y5 receptor agonists at 1 and 5 ng/g given alone. Overall, this study demonstrates that NPY acts centrally through Y1 and Y5 receptors to stimulate food intake in goldfish. The Y1 and Y5 receptors appear to act independently in the stimulation of food intake in goldfish.

The hypothalamic-pituitary-interrenal axis and the control of food intake in teleost fish.

Although environmental, social and physical stressors have been shown to inhibit food intake and feeding behavior in fish, little is known about the mechanisms that mediate the appetite-suppressing effects of stress. Since the hypothalamic-pituitary-interrenal (HPI) axis is activated in response to most forms of stress in fish, components of this axis may be involved in mediating the food intake reductions elicited by stress. Recent investigations into the brain regulation of food intake in fish have identified several signals with orexigenic and anorexigenic properties. Among these appetite-regulating signals are related neuropeptides that can activate the HPI axis, namely corticotropin-releasing factor (CRF) and urotensin I (UI). Central injections of CRF or UI, or treatments that result in an increase in hypothalamic CRF and UI gene expression, can elicit dose-dependent decreases in food intake that can be reversed by pre-treatment with a CRF-receptor antagonist. Evidence also suggests that cortisol, the end product of HPI activation in most fishes (i.e. Osteichthyes), may be involved in the regulation of food intake. Overall, while elements of the HPI axis may mediate some of the appetite-suppressing effects of stress, it is undetermined how either CRF-related peptides, cortisol, or other elements of the stress response interact with the complex circuitry of the hypothalamic feeding center.

Appetite-suppressing effects of urotensin I and corticotropin-releasing hormone in goldfish (Carassius auratus).

Fish urotensin I (UI), a member of the corticotropin-releasing hormone (CRH) family of peptides, is a potent inhibitor of food intake in mammals, yet the role of UI in the control of food intake in fish is not known. Therefore, to determine the acute effects of UI on appetite relative to those of CRH, goldfish were given intracerebroventricular (i.c.v.) injections of carp/goldfish UI and rat/human CRH (0.2-200 ng/g) and food intake was assessed for a 2-hour period after the injection. UI and CRH both suppressed food intake in a dose-related manner and UI (ED50 = 3.8 ng/g) was significantly more potent than CRH (ED50 = 43.1 ng/g). Pretreatment with the CRH receptor antagonist, alpha-helical CRH(9-41), reversed the reduction in food intake induced by i.c.v. UI and CRH. To assess whether endogenous UI and CRH modulate fish appetite, goldfish were given intraperitoneal implants of the glucocorticoid receptor antagonist, RU-486 (50 and 100 microg/g), or the cortisol synthesis inhibitor, metyrapone (100 and 200 microg/g), and food intake was monitored over the following 72 h. Fish treated with either RU-486 or metyrapone were characterized by a sustained and dose-dependent reduction in food intake. Pretreatment with i.c.v. implants of alpha-helical CRH(9-41) partially reversed the appetite-suppressing effects of RU-486 and metyrapone. In a parallel experiment, the effects of RU-486 (100 microg/g) and metyrapone (200 microg/g) intraperitoneal implants on brain UI and CRH gene expression were assessed. Relative to sham-implanted controls, fish treated with RU-486 or metyrapone had elevated UI mRNA levels in the hypothalamus and CRH mRNA levels in the telencephalon-preoptic brain region. Together, these results suggest that UI is a potent anorectic peptide in the brain of goldfish and that endogenous CRH-related peptides can play a physiological role in the control of fish appetite.

Molecular cloning and expression of a type-two somatostatin receptor in goldfish brain and pituitary.

Somatostatin (SRIF or SS) exerts diverse inhibitory actions through binding to specific receptors. In this study, a SRIF receptor cDNA was cloned and sequenced from goldfish brain using PCR and cDNA library screening. The cDNA encodes a 380-amino acid goldfish type-two SRIF receptor (designated as sst(2)), with seven putative transmembrane domains (TMD) and YANSCANP motif in the seventh TMD, a signature sequence for the mammalian SRIF receptor (sst) family. In addition, the amino acid sequence of the receptor has 61-62% homology to mammalian sst(2), 41-47% homology to other mammalian sst subtypes and 41-43% homology to recently identified fish sst(1) and sst(3) receptors. Both SRIF-14 and [Pro(2)]SRIF-14, two of the native goldfish SRIF forms, but not a putative goldfish SRIF-28, significantly inhibited forskolin-stimulated adenosine 3':5'-cyclic monophosphate (cAMP) release in COS-7 cells transiently expressing goldfish sst(2), suggesting functional coupling of the receptor to adenylate cyclase. None of the three peptides affected inositol phosphate production in the same receptor expression system. Northern blot showed that mRNA for the sst(2) receptor is widely distributed in goldfish brain, and highly expressed in the pituitary. The decrease in pituitary sst(2) mRNA levels following estradiol implantation suggests the presence of a negative feedback mechanism on sst(2) gene expression.

Preprotachykinin gene expression in goldfish brain: sexual, seasonal, and postprandial variations.

Recently, we described the complete nucleotide sequence of gamma-preprotachykinin (gamma-PPT) mRNA and the deduced amino acid sequence of the precursor on the basis of molecular cloning and sequence analysis of cDNA from goldfish brain. In the present study, gamma-PPT gene expression in the brain of goldfish was examined using quantitative Northern blot analysis. The results showed that the gamma-PPT gene is highly but differentially expressed in the olfactory bulbs, hypothalamus, and posterior brain regions. There are sexual dimorphism and seasonal variations in gamma-PPT gene expression. In addition, the postprandial changes in gamma-PPT gene expression in the olfactory bulbs and hypothalamus suggest that tachykinin peptides are involved in regulation of feeding behavior in goldfish.

Characterization and distribution of somatostatin binding sites in goldfish brain.

Somatostatin (SRIF) binding sites were characterized in goldfish brain. Binding of (125)I-[Tyr(11)]-SRIF-14 to a brain membrane preparation was found to be saturable, reversible, and time-, temperature-, and pH-dependent. Binding was also displaceable by different forms of SRIF. Under optimal conditions (22 degrees C, pH 7.2), the equilibrium binding of (125)I-[Tyr(11)]-SRIF-14 to goldfish brain membranes was achieved after 60 min incubation. Analysis of saturable equilibrium binding revealed a one-site model fit with K(a) of 1.3 nM. SRIF-14, mammalian SRIF-28, and salmon SRIF-25 displaced (125)I-[Tyr(11)]-SRIF-14 binding with similar affinity, whereas other neuropeptides, e.g., substance P, were unable to displace (125)I-[Tyr(11)]-SRIF-14. Autoradiography studies demonstrated that (125)I-[Tyr(11)]-SRIF-14 binding sites are found throughout the goldfish brain. A high density of (125)I-[Tyr(11)]-SRIF-14 binding sites was found in the forebrain, including the nucleus preopticus, nucleus preopticus periventricularis, nucleus anterioris periventricularis, nucleus lateralis tuberis, nucleus dorsomedialis thalami, nucleus dorsolateralis thalami, nucleus ventromedialis thalami, and nucleus diffusus lobi inferioris. In midbrain, (125)I-[Tyr(11)]-SRIF-14 binding sites were found in the optic tectum. The facial and vagal lobes and the mesencephalic-cerebellar tract were found to have a high density of binding sites. This study provides the first characterization and distribution of specific binding sites for SRIF in a fish brain.

Expression of three distinct somatostatin messenger ribonucleic acids (mRNAs) in goldfish brain: characterization of the complementary deoxyribonucleic acids, distribution and seasonal variation of the mRNAs, and action of a somatostatin-14 variant.

In this study, three somatostatin (SRIF) complementary DNAs (cDNAs) were characterized from goldfish brain. The cDNAs encode three distinct preprosomatostatins (PSS), designated as PSS-I, PSS-II, and PSS-III. The goldfish PSS-I, PSS-II, and PSS-III contain enzymatic cleavage recognition sites, potentially yielding SRIF-14 with sequence identical to mammalian SRIF-14, SRIF-28 with [Glu1, Tyr7, Gly10]SRIF-14 at its C-terminus, and [Pro2]SRIF-14, respectively. The brain distribution of the three SRIF messenger RNAs (mRNAs) were differential but overlapping in the telencephalon, hypothalamus and optic tectum-thalamus regions. Seasonal variations in the levels of the three mRNAs were observed, with differential patterns between the three mRNAs and differences between the sexes. However, only the seasonal alteration in the levels of the mRNA encoding PSS-I showed close association with the seasonal variation in brain contents of immunoreactive SRIF-14 and inversely correlated with the seasonal variation in serum GH levels described in the previous studies, suggesting that SRIF-14 is involved in the control of the seasonal variation in serum GH levels. The putative SRIF-14 variant, [Pro2]SRIF-14, inhibited basal GH secretion from in vitro perifused goldfish pituitary fragments, with similar potency to SRIF-14; [Pro2]SRIF-14 also inhibited stimulated GH release from the pituitary fragments, supporting that [Pro2] SRIF-14 is a biologically active form of SRIF in goldfish.

Postprandial, seasonal and sexual variations in cholecystokinin gene expression in goldfish brain.

Recently, we described the complete nucleotide sequence of cholecystokinin (CCK) mRNA and the deduced amino acid sequence of the precursor on the basis of molecular cloning and sequence analysis of cDNA from goldfish brain. In this study, we investigated the hypothesis that CCK has a role in feeding behavior by examining CCK gene expression in the brain of goldfish using Northern blot. We showed that CCK gene is widely but differentially expressed in broad areas of the goldfish brain, including the olfactory bulbs, telencephalon and preoptic region, hypothalamus, optic tectum-thalamus and posterior brain regions, with highest levels in hypothalamus. We found that CCK mRNA levels in goldfish olfactory bulbs, telencephalon-preoptic region, optic tectum-thalamus, and posterior brain were influenced by sex at least sometime of the seasonal gonadal cycle, with female fish having higher levels than males during at least one of the four seasonal sampling times. We also observed a transient and acute increase in the CCK mRNA levels in the olfactory bulbs, telencephalon-preoptic region, hypothalamus, and posterior brain at 120 min after a meal. These widespread postprandial changes in CCK gene expression in goldfish brain indicate that CCK peptides have multiple roles in regulation of feeding behavior in goldfish. This supports the idea that CCK plays a role as a satiety factor in goldfish.

Characterization and distribution of bombesin binding sites in the goldfish hypothalamic feeding center and pituitary.

Bombesin (BBS)/gastrin-releasing peptide (GRP) binding sites were characterized and their distribution examined in the goldfish brain and pituitary by radioligand binding and autoradiography. Binding of 125I-[Tyr4]-BBS-14 to tissue sections was found to be saturable, reversible, time-dependent and displaceable by BBS/GRP-like peptides. Analysis of saturable equilibrium binding revealed a one-site model fit with a Kd of 0.665 +/- 0.267 nM. This binding site displayed high affinity for members of the BBS subfamily of peptides, including GRP10 (Ki; 0.292 +/- 0.038 nM) and GRP27 (Ki; 2.034 +/- 1.597 nM), but showed no affinity for the BBS8-14 fragment. While an approximate 100-fold lower binding affinity was displayed by the binding site for neuromedin B (Ki; 6.15 +/- 28.2 nM), litorin was highly effective in displacing radiolabeled BBS binding (Ki; 1.469 +/- 0.427 nM). The localization of saturable and high affinity BBS/GRP binding sites in specific areas of the goldfish brain and pituitary generally revealed a similar anatomical distribution to BBS/GRP-like immunoreactive material reported previously by our laboratory. Quantitative densitometric analysis of radiolabeled BBS binding to brain nuclei and the pituitary revealed a moderate concentration of BBS/GRP binding sites in the hypothalamic feeding area, including the nucleus diffusus libi inferioris, nucleus recessus lateralis, nucleus lateral tuberis, and nucleus anterior tuberis. Other brain nuclei known to influence the brain feeding center which contained a high density of BBS/GRP binding sites included nuclei of the dorsal and ventro-medial telencephalon, the preoptic hypothalamus, and the optic tectum. High densities of BBS/GRP binding sites were also localized in the dorsal cerebellum, and nucleus habenularis. In the pituitary, BBS/GRP binding sites were present in high concentration in the neurointermediate lobe, with a relatively lower density localized in the pars distalis. The present study further supports a role for BBS/GRP-like peptides in the regulation of feeding behavior and anterior pituitary hormone secretion in teleosts.

The regulatory effects of thyrotropin-releasing hormone on growth hormone secretion from the pituitary of common carp in vitro.

The effects of thyrotropin-releasing hormone (TRH) on growth hormone (GH) and gonadotropin (GtH) release, and the influences of somatostatin (SRIF), the dopamine agonist apomorphine (APO) and extracellular calcium on basal and TRH-induced GH release were examined using an in vitro perifusion system for pituitary fragments of common carp (Cyprinus carpio). Five minute pulses of different dosages of TRH stimulated a rapid and dose-dependent increase in GH release from the perifused pituitary fragments with an ED50 of 9.7 ± 2.3 nM. TRH was ineffective on GtH release. SRIF significantly inhibited basal and TRH-induced GH release from the perifused pituitary fragments, and the effects of SRIF were dose-dependent. APO induced a dose-dependent increase in basal and TRH-stimulated GH release from the perifused pituitary fragments. Increasing the concentrations of extracellular calcium from 0 mM to 1.25 mM resulted in an increase in basal and TRH-induced GH release. The high dose of calcium (6.25 mM) caused a slight decrease in basal and TRH-induced GH release compared with those at a concentration of 1.25 mM.

Isolation and characterization of hypothalamic growth-hormone releasing factor from common carp, Cyprinus carpio.

A growth hormone-releasing factor (GRF)-like peptide was isolated from the hypothalamus of common carp, Cyprinus carpio, by acid extraction, gel filtration chromatography, immunoaffinity chromatography using antiserum directed against rat GRF, and multiple steps of HPLC using octadecyl columns. Based on Edman degradation and peptide mapping, this teleost GRF was established to be a 45-residue peptide with the following primary structure: His-Ala-Asp-Gly-Met-Phe-Asn-Lys-Ala-Tyr-Arg-Lys-Ala-Leu-Gly-Gln-Leu-Ser- Ala-Arg - Lys-Tyr-Leu-His-Thr-Leu-Met-Ala-Lys-Arg-Val-Gly-Gly-Gly-Ser-Met-Ile-Glu- Asp-Asp-Asn-Glu-Pro-Leu-Ser. Carp GRF is closely related structurally to peptides of the glucagon-secretin superfamily, and more particularly to mammalian vasoactive intestinal peptide (VIP) precursors and the N-terminal portion of mammalian GRFs. A synthetic replicate of this peptide is highly potent [50% effective dose (ED50) approximately 0.08 nM] in stimulating GH release from cultured goldfish pituitary glands and in elevating serum GH levels 30 min after injection (0.1 micrograms/g) in goldfish.

Influence of GABA on gonadotrophin release in the goldfish.

The influence of GABA on pituitary gonadotrophin (GTH) release in the goldfish was studied by means of in vivo and in vitro techniques. It was found that GABA injected intraperitoneally caused an increase of serum GTH levels in regressed or early maturing fish, but not in late maturing animals. Moreover, injection of a GABA transaminase inhibitor caused a significant increase of GABA within the hypothalamus and pituitary, and a dose-dependent increase in serum GTH levels. To determine if this effect could be exerted directly at the level of the pituitary, dispersed pituitary cells in static incubation or in perifusion were exposed to increasing concentrations of GABA or its agonists muscimol and baclofen. None of these drugs was able to modify the spontaneous or GnRH-induced secretion of GTH, indicating that the in vivo effect of GABA was most likely mediated via another hypothalamic factor. Using in vitro incubation of pituitary slices, it was found that GABA caused a dose-related stimulation of GnRH release at the level of the pituitary, providing a possible explanation for the observed in vivo stimulatory effect of GABA on GTH release. Since the seasonal effect of GABA in vivo indicated a possible interaction of GABA with sexual steroids, GABA was given intraperitoneally to female goldfish implanted with either testosterone or estradiol. We found that the stimulatory effect of GABA on GTH release was abolished in estradiol-treated females but was still observed in testosterone-implanted fish. Moreover, estradiol but not testosterone caused a decrease of the GABA concentration within the telencephalon.(ABSTRACT TRUNCATED AT 250 WORDS)

Selective depletion of dopamine in the goldfish pituitary caused by domperidone.

The effects of the dopamine type-2 receptor (D-2) antagonist domperidone on pituitary and brain amine concentrations and serum gonadotropin levels in the goldfish were investigated. Domperidone caused a long-lasting, dose-dependent depletion of dopamine in the goldfish pituitary. Pituitary concentrations of 5-hydroxytryptamine (5HT) were unaffected by domperidone treatment. Concentrations of noradenaline, dopamine, and 5HT in the hypothalamus and telencephalon were also unaffected by domperidone treatment. In contrast to the goldfish, dopamine levels in both mouse pituitary and hypothalamus were unaffected by domperidone treatment. The depletion of dopamine was observed in both sexually regressed and recrudescent, male and female fish, but elevation of serum gonadotropin levels in response to domperidone treatment occurred only in sexually recrudescent fish. Treatment of sexually recrudescent fish with the D-2 antagonists pimozide, (-)-sulpiride and eticlopride and the dopamine type-1 (D-1) antagonists SKF 83566 and SCH 23390 failed to elicit a depletion of pituitary dopamine or elevation of serum gonadotropin. Treatment of sexually recrudescent fish with domperidone, alpha-methyl-p-tyrosine or carbidopa elicited comparable depletions of pituitary dopamine and elevations of serum gonadotropin. The results suggest that in addition to D-2 receptor antagonist activity, domperidone has some other neuropharmacological action on dopaminergic neurones in the goldfish pituitary.

Increased gonadotropin levels in goldfish do not result in alterations in circulating thyroid hormone levels.

To determine whether increases in gonadotropin levels are capable of altering thyroid function in goldfish, plasma thyroid hormone levels were measured following induced changes in endogenous gonadotropin secretion and injection of carp gonadotropin. Radio-frequency lesions placed in the nucleus preopticus periventricularis or monosodium-L-glutamate-induced lesions of the posterior nucleus lateralis tuberis (NLT) of the hypothalamus were capable of stimulating significant increases in plasma gonadotropin levels, but were without effect on plasma triiodothyronine (T3) or thyroxine (T4) at time intervals ranging from 5 hr to 10 days. Likewise, injections of a superactive analog of gonadotropin-releasing hormone resulted in profound increases in gonadotropin levels without associated changes in thyroid hormones. No changes in the circulating levels of T4 or T3 were observed in response to injection of purified carp gonadotropins whereas injection of bovine thyrotropin or carp pituitary extracts stimulated significant increases in T4. Radiofrequency lesions of the pituitary stalk or of the anterior NLT also resulted in significant increases in circulating levels of T4, but not of T3, at 10 and 30 hr postlesion. These results demonstrate that direct acute stimulation of circulating thyroid hormone levels is not an intrinsic action of endogenous goldfish gonadotropin and that activation of the reproductive system, leading to ovulation in some cases, is without effect on blood total thyroid hormone levels. Additionally, these results confirm that hypothalamic inhibition of the pituitary-thyroid axis exists in this teleost fish and demonstrate that interruption of this inhibition results in a time-dependent, high-magnitude increase in circulating thyroxine levels.

Effects of forebrain lesions on spawning behaviour in the male goldfish.

Lesions were stereotaxically placed in medial nuclei of the ventral telencephalon and preoptic area of male goldfish. Only lesions in the area ventralis telencephali pars supracommissuralis (Vs) and posterior pars ventralis (pVv) were effective in reducing the proportion of males spawning, as compared to sham groups, both 5 days (Experiment 1) and up to 4 weeks (Experiment 2) postoperatively. Spawning consistency over 7 weekly tests was negatively correlated with the volume of Vs-pVv destruction. Two-thirds of Vs-pVv lesioned males spawned on at least one of their weekly tests, with latencies for the onset of each courtship behaviour similar to those of control fish, partial performance of the spawning sequence was rare. These results suggest that lesion of the supracommissural telencephalon (Vs-pVv region) blocks the initiation of spawning behaviour in the male goldfish, perhaps by lowering reproductive motivation specifically or by interfering with the perception of sexual, particularly olfactory, cues.

Effects of brain lesions of gonadotrop ultrastructure and serum gonadotropin levels in goldfish.

Brain lesions that destroyed the anterior preoptic region or the pituitary stalk in sexually mature (= completed ovarian recrudescence) goldfish caused a significant increase in serum gonadotropin levels for at least 11 days postoperatively. These results confirmed previous findings indicating the presence of a gonadotropin release-inhibitory factor. Electron-microscopic investigation revealed that the gonadotrops were depleted of the small secretory granules, had marked dilations of the cisternae of the endoplasmic reticulum and extensive development of the Golgi apparatus. This indicated both secretion and synthesis, and correlated with the prolonged increase in serum gonadotropin resulting from the lesions.

Involvement of the preoptic region in gonadotropin release-inhibition in goldfish, Carassius auratus.

Lesions were made in various hypothalamic and preoptic regions in sexually mature female and male goldfish. Destruction of the pituitary stalk, and lateral anterior hypothalamic tract areas caused ovulation and increased serum gonadotropin levels. Destruction of the entire preoptic region or a major part of the anterior nucleus preopticus periventricularis also caused ovulation and increased serum GtH levels. Lesions in other locations were ineffective. The results indicate that a gonadotropin release-inhibitory factor (GRIF) probably originates in the anterior preoptic region, and reaches the pituitary via pathways in the lateral preoptic and lateral anterior hypothalamic regions, and the pituitary stalk. The preovulatory surge of gonadotropin secretion may be regulated by release from inhibition exerted by GRIF in goldfish.

Brain lesions and short-term endocrine effects of monosodium L-glutamate in goldfish, Carassius auratus.

Monosodium L-glutamate (MSG) was injected intraperitoneally into goldfish at a dosage of 2.5 mg/g body weight. At 24 h post-injection there was a marked hypertrophy and edema in the region of the nucleus lateralis tuberis (NLT) from the anterior margin of the pituitary stalk through to the posterior end of the NLT, irrespective of the sex of the goldfish. A similar hypertrophy and edema occurred ventral to the anterior commissure in the preoptic region in the anterior-ventral nucleus preopticus periventricularis (NPP). At 6 h post-injection a slight vacuolization was evident in these two regions, and at two days the hypertrophy and edema had abated from the extent observed at 24 h post-injection. At five and eight days post-injection only necrotic cells were found in the affected NLT region, but only a small band of necrotic cells was evident in the anterior-ventral preoptic region. No other brain lesions were evident. Serum levels of gonadotropin (GtH) were increased at 6 h, 24 h, and two days after treatment with MSG, but were similar to control values at five, seven and eight days after MSG in male and female goldfish. Exocytosis of small dark secretory granules in gonadotrophs was evident at 24 h after MSG in a fish with a somewhat greater increase in serum GtH than usually found. The time course of increased serum GtH levels postinjection of MSG is consistent with the observed time course of hypertrophy and atrophy of NLT neurons; the increase in serum levels of GtH is interpreted to reflect a stimulation of release of GtH-releasing factor from neurons in the NLT. Electron microscope investigation indicates that prolactin cells have increased secretory and synthetic activity from 24 h through to seven days post-injection of MSG. The mechanism for stimulation of the prolactin cells by MSG is not known. No other changes in activity of adenohypophysial secretory cells were found.