Preoptic-anterior Hypothalamic Area Research Articles

Aromatase, 5 alpha- and 5 beta-reductase in brain, pituitary and skin of the sex-role reversed Wilson's phalarope.

While intrasexual competition for mates is generally considered to be an androgen-dependent characteristic of reproductively active males, in the Wilson's phalarope (Phalaropus tricolor) it is the female that acquires the brighter nuptial plumage and aggressively competes for access to the less aggressive males. Despite this pronounced sex-role reversal, circulating sex steroid hormones of breeding phalaropes are similar to those of avian species displaying traditional male-female reproductive roles. To investigate whether these behavioural and morphological steroid-dependent differences may be due to differences in target organ metabolism of circulating androgen, [3H]androstenedione in the presence of an NADPH-generating system was incubated with homogenates of brain, pituitary and skin of male and female Wilson's phalaropes collected from a naturally breeding population. Oestrone, 5 alpha-androstanedione and 5 beta-androstanedione were measured as endpoints of aromatization, 5 alpha-reduction and 5 beta-reduction respectively. Aromatase activity in the anterior hypothalamus/preoptic area (AHPOA) and posterior hypothalamus was greater in breeding males with high circulating concentrations of testosterone than in females, and activity in the AHPOA was greater in breeding than in non-breeding males (with low circulating testosterone). Aromatase levels did not differ in septum, archistriatum, hyperstriatum or pituitary. 5 alpha- and 5 beta-reductase were detected in all neuroendocrine tissues sampled and although there were no significant male-female differences, 5 alpha-reductase was greater in the AHPOA of breeding than of nonbreeding males.(ABSTRACT TRUNCATED AT 250 WORDS)

Estrogen Alters Oxytocin mRNA Levels in the Preoptic Area

Abstract Estrogen has numerous effects on immunoreactive levels of oxytocin (OXT) centrally, particularly in the preoptic lateral subcommissural nucleus (LSN). In this study in situ hybridization of a 38-base oligodeoxyribonucleotide (38mer) complementary to OXT mRNA revealed that estrogen treatment altered the pattern of OXT production in the rostral LSN and the more caudal anterior commissural nucleus. Rats were injected with 20 ng estradiol benzoate or sesame oil vehicle im 4 and 5 days after ovariectomy. On the sixth day all animals were perfused with paraformaldehyde-glutaraldehyde and their brains sectioned to 10 mum thickness in a -10 degrees C cryostat. Coronal brain sections were taken from four parallel levels of the preoptic-anterior hypothalamic area. These sections were mounted and hybridized in situ to a [l(125)]-labeled 38mer for 16 h at 37 degrees C. Washed and dried slides were processed for autoradiography and analyzed with a light microscope. The effect of estrogen on OXT production differed between the rostral and caudal sections in both the LSN and periventricular (PeV) areas. Estrogen significantly increased OXT mRNA levels in LSN cells while decreasing hybridization in the anterior commissural nucleus cells. Changes in frequency patterns in the PeV paralleled those in the LSN with a significant drop of hybridization in the caudal PeV. Neurons hybridizing 38mer probe were also found in several other areas including the ventral medial preoptic area, lateral hypothalamus, bed nucleus of the stria terminalis and the nucleus triangularis septi. OXT mRNA levels were affected by estrogen treatments and this effect differed between the preoptic area and anterior hypothalamus. The sensitivity of LSN oxytocinergic cells to estrogen has implications for estrogen-sensitive OXT-enhanced reproductive behaviors.

In vitro localization of thermosensitive neurons in the rat diencephalon.

Many thermosensitive neurons in the preoptic area-anterior hypothalamus (POAH) are believed to function in thermoregulation. Although many other diencephalic regions are implicated in thermoregulation, measurements of single-cell activity during localized thermal stimulation in these regions are lacking. Utilizing horizontal tissue slices, we have recorded single-unit activity throughout the rat diencephalon in response to localized thermal stimulation. Thermosensitive cells were identified in 18 nuclei. The proportions of each subpopulation inside vs. outside the POAH were similar: POAH (n = 83 cells); warm = 31%, cold = 4%, warm-cold = 1%, and temperature insensitive = 64%, outside POAH (n = 198 cells; warm = 39%, cold = 6%, warm-cold = 4%, and temperature insensitive = 51%. However, nuclei located rostral and lateral to POAH contained a large percentage of warm-sensitive cells (49-63%). Caudal nuclei contained approximately half of the cold-sensitive cells studied. This wide distribution of thermo-sensitive cells suggests that many diencephalic areas, besides the POAH, are capable of thermoreception and thermointegration. Moreover, many of these thermosensitive cells may function in other systems (e.g., reproduction, feeding, and water balance) which central and environmental temperatures are known to influence.

Effects of synaptic blockade on thermosensitive neurons in rat diencephalon in vitro.

To identify the distribution of inherently thermosensitive and conditionally (i.e., synaptically dependent) thermosensitive neurons in the rat diencephalon, single-unit recordings (n = 88) were made in horizontal tissue slices during localized thermal stimulation before, during, and after reversible synaptic blockade. Inherently warm-sensitive neurons (n = 17) were found in 10 nuclei, the largest number occurring in the preoptic area-anterior hypothalamus (POAH). Inherently cold-sensitive neurons (n = 5) were encountered in three nuclei, with the highest number in the posterior hypothalamus (PH) and mammillary body (MB). Fifty-nine percent of the inherently thermosensitive neurons showed a change in spontaneous activity and/or thermosensitivity during synaptic blockade, indicating that these neurons undergo synaptic modulation. Conditionally warm-sensitive neurons (n = 14) were found in six nuclei with the majority of these neurons located in the accumbens nucleus, diagonal band of Broca, and PH-MB. Two conditionally cold-sensitive neurons were found in the POAH and one in the MB. Temperature-insensitive neurons (n = 49) were rarely affected by synaptic blockade. Thus inherently and conditionally thermosensitive neurons are found in many locations in the diencephalon. These thermosensitive neurons may belong to the neuronal networks responsible for thermo-regulation and the other homeostatic systems that are influenced by temperature.

Coordination of hamster lordosis and flank marking behavior: Role of arginine vasopressin within the medial preoptic-anterior hypothalamus

The role of arginine vasopressin (AVP) within the medial preoptic area-anterior hypothalamus (MPOA-AH) in the neural coordination of lordosis and flank marking was investigated. AVP, but not saline, microinjected into the MPOA-AH of ovariectomized hamsters not given hormone replacement therapy stimulated high levels of flank marking when tested with a sexually experienced male, or when tested alone. In contrast, AVP microinjected into the MPOA-AH of ovariectomized hamsters given estradiol benzoate (EB) and progesterone did not stimulate flank marking or inhibit lordosis during tests with a sexually experienced male. However these same females exhibited high levels of flank marking in response to AVP when tested alone. A second experiment demonstrated that progesterone was not required for inhibition of AVP-induced flank marking in ovariectomized females given EB replacement and tested with sexually experienced males. The present study provides no evidence that AVP acts within the MPOA-AH to inhibit hamster lordosis, but demonstrates that ovarian hormones and male social contact block the induction of flank marking by AVP microinjected into the MPOA-AH. These data suggest that one component in the neural coordination of lordosis and flank marking is inhibition of the response of the MPOA-AH to AVP.

Effects of intracranial implantation of dihydrotestosterone on sexual behavior in male Cnemidophorus inornatus, a direct sexual ancestor of a parthenogenetic lizard

Dihydrotestosterone was implanted directly into the brain of castrated male Cnemidophorus inornatus, a direct sexual ancestor of the parthenogenetic species C. uniparens. Only implants located in the anterior hypothalamus-preoptic area (AH-POA) induced male-typical sexual behavior. Implants in other brain regions, including the ventromedial hypothalamus, failed to elicit courtship or copulatory behavior. Radioimmunoassay revealed no significant difference in the concentrations of circulating androgens between the responding and nonresponding animals. Previous data from this laboratory demonstrated that the AH-POA controls malelike pseudosexual behavior in C. uniparens. The current results support the hypotheses that (i) the AH-POA is the major area of hormone action in the brain controlling male-typical sexual behavior in C. inornatus as in other vertebrates and (ii) the neural circuits controlling male-typical behavior have been conserved in the evolution of the parthenogen C. uniparens.

Hypothalamic somatostatin may mediate endotoxin-induced fever in the rat

(1) The changes in rectal temperature produced by an injection of a bacterial endotoxin piromen (10-40 ng in 1.0 microliter) on somatostatin-14 (SS-14; 0.1-0.3 microgram in 1.0 microliter) into the preoptic anterior hypothalamic area were assessed and compared in control rats, in rats with hypothalamic SS depletion, and in rats with hypothalamic SS receptor blockade. (2) Intrahypothalamic injection of either piromen or SS-14 produced a dose-related rise in rectal temperature in intact, control rats. The fever induced by intrahypothalamic injection of piromen or SS-14, as well as that induced by intraperitoneal injection of piromen, was antagonized by pretreatment of the hypothalamus with a SS-14 receptor antagonist (0.1 ng in 1.0 microliter) in rats. (3) On the other hand, intraperitoneal administration of cysteamine (30-100 mg/kg), in addition to producing a dose-related fall in rectal temperature, also caused a dose-related fall in hypothalamic SS-levels in rats. Furthermore, the fever induced by intrahypothalamic injection of piromen, but not SS-14, was antagonized by depletion of hypothalamic SS levels with an intraperitoneal dose of cysteamine (30 mg/kg). (4) The results indicate that a somatostatinergic pathway in the hypothalamus may mediate endotoxin-induced fever in the rat.

Direct hypothalamic control of vasoactive intestinal peptide (VIP) levels in the developing rat ovary

We have previously identified the neurotransmitter vasoactive intestinal peptide (VIP) in nerve fibers of the immature rat ovary and showed that it stimulates steroid release by a mechanism involving increased synthesis of the components of the cholesterol side-chain cleavage enzyme complex. The present experiments were undertaken to study the ontogeny of ovarian VIP levels and to determine if they change in relation to the initiation of puberty. VIP was already detected in 2-day-old ovaries; levels remained constant at approximately 4.5 pg/mg ovary until the end of juvenile development (day 30). Thereafter, and preceding the peripubertal activation of the ovary, VIP levels increased two-fold, decreased gradually towards the first proestrus, and returned to juvenile values after the first ovulation. Transection of the ovarian nerves eliminated radioimmunoassayable VIP levels in both intact and hypophysectomized rats, indicating that ovarian VIP derives mostly from the extrinsic innervation of the gland. Treatment of hypophysectomized immature female rats with human chorionic gonadotropin (hCG), follicle stimulating hormone (FSH), growth hormone (GH), prolactin (Prl), estradiol, or their combination, failed to reproduce the peripubertal increase in VIP. In contrast, unilateral direct anodal current lesions of the left preoptic-anterior hypothalamic area (POA-AHA) of hypophysectomized juvenile rats led to a significant increase in VIP in the ipsilateral ovary. Surprisingly, both bilateral lesions and lesions of the right POA-AHA also increased VIP levels in the left ovary suggesting the existence of a marked asymmetry in the hypothalamic control of ovarian VIP. Lesions of the ventromedial nucleus, dorsal AHA or small lesions of the AHA were ineffective. The results suggest that: a) in prepubertal rats ovarian VIP levels are controlled by a pituitary-independent, neurally-mediated, mechanism which involves the POA-AHA region of the hypothalamus; b) this control is markedly asymmetric; and c) the lesion-induced increase in ovarian VIP levels may not result from the loss of a discrete inhibitory center, but rather may be the consequence of compensatory reactivity of the areas surrounding the lesion.

Somatostatin: a hypothalamic transmitter for thermoregulation in rats

The changes in both the thermoregulatory responses and brain somatostatin (SS) levels produced by ambient temperature (Ta) changes were assessed in rats after they had been equilibrated to each of the Ta for a period of about 90 min. Cold exposure, in addition to elevating hypothalamic SS-levels, led to increased metabolism and cutaneous vasoconstriction at Ta = 8 degrees C. In contrast, heat exposure, in addition to lowering hypothalamic SS-levels, resulted in decreased metabolism and cutaneous vasodilation at Ta = 30 degrees C. Rats were chronically implanted with a hypothalamic cannula to allow intrahypothalamic injection of SS on the conscious rats. Direct administration of SS (0.1-0.3 micrograms) into the preoptic anterior hypothalamic area caused a dose-related rise in colon temperature at three Ta tested. The SS-induced hyperthermia was produced by increased metabolism at Ta = 8 degrees C, whereas at Ta = 30 degrees C, it was caused by cutaneous vasoconstriction. At Ta = 22 degrees C, the hyperthermia was caused by increased metabolism and cutaneous vasoconstriction. Systemic administration of cysteamine, in addition to lowering hypothalamic SS-levels, produced a dose-related fall in colon temperature at Ta of 8 degrees C and 22 degrees C. The hypothermia induced by cysteamine was produced by decreased metabolism at Ta = 8 degrees C, whereas at Ta = 22 degrees C, it was caused by both decreased metabolism and cutaneous vasodilation. The data indicate that the hypothalamic SS-levels mediate normal body temperature responses in rats.

Two sexually dimorphic cell groups in the human brain

A quantitative analysis of the volume of 4 cell groups in the preoptic-anterior hypothalamic area (PO-AHA) and of the supraoptic nucleus (SON) of the human brain was performed in 22 age-matched male and female individuals. We suggest the term Interstitial Nuclei of the Anterior Hypothalamus (INAH 1-4) to identify these 4 previously undescribed cell groups in the PO-AHA. While 2 INAH and the SON were not sexually dimorphic, gender-related differences were found in the other 2 cell groups. One nucleus (INAH-3) was 2.8 times larger in the male brain than in the female brain irrespective of age. The other cell group (INAH-2) was twice as large in the male brain, but also appeared to be related in women to circulating steroid hormone levels. Since the PO-AHA influences gonadotropin secretion, maternal behavior, and sexual behavior in several mammalian species, these results suggest that functional sex differences in the hypothalamus may be related to sex differences in neural structure.

Intrahypothalamic actions of somatostatin and growth hormone releasing factor on growth hormone secretion.

Possible effects of GRF on somatostatin neurons and of somatostatin on GRF neurons were examined by measuring the effects of localised intracerebral injections of these peptides on growth hormone (GH) secretion. Serial GH concentrations were measured in plasma in unanaesthetized male rats chronically prepared with venous and intracerebral cannulae, before and after treatment with bilateral intracerebral injections of somatostatin or GRF in the preoptic anterior hypothalamic area (PO/AHA) and medial basal hypothalamus. Injections of 0.1 and 1 nmol of GRF in medial basal hypothalamus or 10 nmol somatostatin in the PO/AHA, respectively, had stimulatory or inhibitory effects on GH, which were assumed to be due to diffusion of the peptide from the injection site to the median eminence and pituitary gland. Injection of lower doses of somatostatin around GRF neurons in the medial basal hypothalamus were without significant effect on secretion of GH, but 0.1 nmol somatostatin in the PO/AHA resulted in an increase in GH concentrations from 128 +/- 61 to 524 +/- 103 ng/ml, p less than 0.02. Injections of GRF in lower doses amongst somatostatin neurons in the PO/AH or amongst GRF neurons in the medial basal hypothalamus were both without effect on GH secretion. We conclude that somatostatin may stimulate GH secretion by an effect on or close to somatostatin neurons in the PO/AHA. Somatostatin, though present in terminals on GRF neurons, is without effect at this site in our model. Furthermore, we have been unable to demonstrate any significant intrahypothalamic effect of GRF on GH regulation.

Aromatase activity in quail brain: correlation with aggressiveness.

Testosterone (T) triggers aggressive behavior in males of many vertebrate species; however, the neural and hormonal basis of individual differences in the frequency or intensity of aggressive behavior is still debated. Using the Japanese quail (Coturnix coturnix japonica), a species in which individuals exhibit a wide range of aggressiveness in nature and the laboratory, together with a newly devised test procedure for quantifying aggressiveness, we recently demonstrated that aggression is estrogen dependent. Here we extend these studies by testing the hypothesis that aromatization in brain is a rate-limiting step in the expression of individual differences in aggressiveness. Using procedures previously validated for this species, aromatase and 5 alpha- and 5 beta-reductase activities were estimated in selected brain regions of reproductively active male quail by measuring conversion of [3H]androstenedione to [3H]estrone, [3H]5 alpha-androstanedione, and [3H]5 beta-androstanedione, respectively. In Exp 1, behaviorally inexperienced test birds were killed 90 sec after a single behavioral test. Aggressiveness of individuals in this group, as determined by pecking and locomotor activity in response to visualization of a conspecific, ranged 3- to 4-fold from high to low. Aromatase activity in the posterior hypothalamus (PHYP) was significantly higher in males rated high for aggressiveness than in animals rated low (1.04 vs. 0.59 pmol/h.mg protein; P less than 0.02). Similar differences were observed in the anterior hypothalamus/preoptic area (AHPOA) but were not significant. In Exp 2, sexually mature males were behaviorally tested eight times over 22 days and killed 24 h after the final test. Aggressiveness varied 5-fold from high to low, although the rating in a given bird remained constant with time and repeat testing. Aromatase activity in the AHPOA was significantly greater in birds rated high for aggressiveness than in low aggressiveness birds (3.77 vs. 2.80 pmol/h.mg protein; P less than 0.02). In addition, when AHPOA aromatase in all birds was plotted against behavioral intensity, there was a 2-fold variation and a significant positive correlation (r = 0.556; P less than 0.02). Similar differences were observed in PHYP, but these were of borderline significance. By contrast, aromatase levels outside the AHPOA and PHYP were unrelated to behavior. Moreover, in both Exp 1 and 2, 5 alpha- and 5 beta-reductase activities in AHPOA, PHYP, and other brain regions; plasma T, 5 alpha-dihydrotestosterone, and total estrogens; and relative testicular weights were not consistently related to aggression.(ABSTRACT TRUNCATED AT 400 WORDS)

Recovery of preoptic–anterior hypothalamic functions after transplantation

Kainic acid lesion of the medial preoptic area resulted in the impairment of the thermoregulation and disruption of the reproductive cycle in female rats. The preoptic-anterior hypothalamic area from fetal donor was transplanted into the lesioned area ofthe host. After transplantation, these animals showed signs of estrus cyclicity and a recovery in basal temperature towards normal. They also showed a reduced shift of body temperature on exposure to a hot environment. Thus the female rats, which received transplantation, showed some degree of recovery of functions which were disrupted by kainic acid lesions.

Responses of anterior hypothalamic-preoptic thermosensitive neurons to thyrotropin releasing hormone and cyclo(his-pro)

Effects of local application of thyrotropin releasing hormone (TRH) and its metabolite, histidyl-proline diketopiperazine [cyclo (His-Pro)], on the activity of thermosensitive and thermallyinsensitive neurons of the anterior hypothalamic-preoptic area were investigated in urethane-anesthetized rats. Microelectrophoretic application of TRH changed the activity of 126 of 206 neurons tested. Thyrotropin releasing hormone predominantly decreased the activity of warm-sensitive neurons and increased the activity of cold-sensitive neurons. Since it has been generally assumed that warm-sensitive and cold-sensitive neurons in the anterior hypothalamic-preoptic area mediate heat and cold defence responses, respectively, the present results are consistent with previous findings showing hyperthermia after injection of TRH into the hypothalamus in the rat. Cyclo (His-Pro) affected the activity of 59 of 153 neurons tested. In addition, cyclo (His-Pro) did not preferentially affect warm- or cold-sensitive neurons. These results indicate that the previously-determined hypothermie effect of cyclo (His-Pro) cannot be explained by its effects on thermosensitive neurons in the anterior hypothalamic-preoptic area.

Temperature-related release of serotonin from unrestrained rats' pre-optic area perfused with ethanol

The circumscribed effect of ethyl alcohol on the local efflux of serotonin (5-HT) within the thermosensitive region of the anterior hypothalamic, pre-optic area (AH/POA) of the unrestrained rat was examined in relation to core temperature. A single guide cannula for push-pull perfusion was implanted stereotaxically in the AH/POA within coronal planes AP 7.0–8.2. Following 3–4 push-pull perfusions with control artificial CSF of a site identified as reactive to 5-HT, ethanol in a concentration of 2.75 (471 mM) or 5.5 (942 mM) percent was perfused at the same locus over a 5–10 min interval. Successive samples of perfusate were assayed for their content of 5-HT by high performance liquid chromatography using electrochemical detection (HPLC-EC). Within a circumscribed region of the AH/POA of the rat maintained at an ambient temperature of 22°C, ethanol induced either an immediate or delayed hypothermia of short latency or a transient decline followed by an immediate increase in core temperature. In each case, the shift in temperature depended on the anatomical site of push-pull perfusion. Overall, the fall in core temperature was accompanied by an inhibition in the efflux of 5-HT. However, the consequent rise in the rat's core temperature was associated with an enhanced release of 5-HT in the samples of perfusate collected from the AH/POA. These results suggest that serotonergic synapses within the AH/POA are apparently involved in the thermolytic effects of ethanol as well as in the thermogenesis following the interval of heat loss.

In vivo release rates of substance P in the preoptic/anterior hypothalamic area of ovariectomized and ovariectomized estrogen-primed rats: Correlation with luteinizing hormone and prolactin levels

Push-pull cannulae were implanted into the preoptic/anterior hypothalamic area (POA) of ovariectomized (OVX) rats. After recovery animals were treated with estradiol (E 2) or corn oil and they were perfused 3 days later. Substance P (SP) concentrations were measured in 15 min perfusate fractions, blood samples were taken at similar intervals. SP concentrations in POA perfusates were readily measurable. Following estrogen priming SP release increased significantly each afternoon prior to the estrogen induced prolactin and luteinizing hormone (LH) surges. No such increase of SP release was observed in OVX rats with constant LH and prolactin levels throughout the day. Mean SP release rates in OVX rats were significantly higher in comparison to OVX estrogen-primed rats. These results indicate that SP may be involved in the feedback mechanisms of estrogen on prolactin and LH release. Authenticity of SP in POA perfusates was made probable by high-performance liquid chromatography (HPLC) where synthetic SP eluted at the same retention time as the signal measured in push-pull perfusates.

Orchidectomy Induces Temporal and Regional Changes in the Processing of the Luteinizing Hormone-Releasing Hormone Prohormone in the Rat Brain

The structures of the complementary DNA (cDNA) that encode the rat and human hypothalamic LHRH prohormones were recently determined and the corresponding amino acid sequences deduced. In addition to the LHRH decapeptide, the prohormone contains a 56-amino acid peptide sequence which has been designated gonadotropin-releasing hormone associated peptide (GAP). In the present study we examined the effect of orchidectomy on LHRH prohormone processing in three brain regions known to contain the various elements of the LHRH neuronal system; the preoptic-anterior hypothalamic area, the hypothalamus (HYP), and the median eminence. Both LHRH-like and GAP-like immunoreactivities (LHRH-LI and GAP-LI) were quantitated in these regions in intact male rats and male rats orchidectomized for 1, 2, 3, 5, 7, 14, or 40 days. In addition, the LHRH and GAP immunoreactivities were localized and the effects of orchidectomy examined using immunocytochemical techniques. One day after orchidectomy, a small decrease in GAP-LI and an increase in LHRH-LI were evident in extracts of the preopticanterior hypothalamic area which resulted in a significant decrease in the GAP/LHRH molar ratio. A similar selective decrease in GAP-LI and in the GAP/LHRH molar ratio was also observed in extracts of the HYP, but not until 2 days after orchidectomy. The GAP/LHRH ratio in both regions gradually returned to that of the intact controls. In both the HYP and median eminence, GAP-LI and LHRH-LI gradually declined in parallel through 14 days after orchidectomy. The gradual loss of immunoreactivity in these regions was evident by both RIA quantification and immunocytochemistry. These observations suggest that 1) production and processing of both LHRH and its prohormone are affected by testicular factors, 2) that divergent enzyme and/or transport systems, regulating LHRH and GAP processing, may exist at the level of the perikarya, and 3) long term orchidectomy results in decreased biosynthesis of the prohormone and/or in parallel increases in LHRH and GAP degradation or transport.

Changes in brain aromatase and 5 alpha-reductase activities correlate significantly with seasonal reproductive cycles in goldfish (Carassius auratus).

Aromatization and 5 alpha-reduction are known to be required for the full expression of testosterone actions in neuroendocrine tissues. Although aromatase and 5 alpha-reductase activities in brain and pituitary can be experimentally manipulated by castration and steroid replacement, naturally occurring variations during seasonal reproductive cycles have not been examined in any species. Goldfish (Carassius auratus) were selected for study because they exhibit exceptionally high levels of aromatase in both brain and pituitary, although 5 alpha-reductase levels resemble the vertebrate norm. Four animals of each sex were tested monthly through three breeding seasons (2.5 yr). Using previously validated techniques, the enzymes were assayed by product formation from [3H]androstenedione in homogenates of anterior hypothalamus-preoptic area (AHPOA), remaining telencephalon (TEL), whole pituitary, ovary, and testis. Seasonal variations in aromatase were most dramatic in the AHPOA of female fish, exhibiting a peak in April and May that was 6-fold higher than the nadir in July. As judged by changes in the appearance and weight of the gonads, maximal aromatase coincided with the spawning season, whereas low enzyme levels corresponded to reproductive inactivity. Seasonal variations were similar but of a lesser magnitude in the TEL of females and in the AHPOA and TEL of males (2- to 3-fold, peak to nadir). Both ovarian and testicular aromatase showed cyclic changes; however, activity was much lower than that in brain at all times of the year (4.5, 1.2, and 47.0 pmol/mg protein, maximal values in ovaries, testes, and AHPOA, respectively). Pituitary aromatase varied from 5-22 pmol/mg protein, but was not consistently correlated with season. Cyclic changes in 5 alpha-reductase were distinctly different from those in aromatase, with maximal values in both brain and pituitary occurring when fish were reproductively inactive. In general, circulating sex steroids were high when aromatase was high and low when reductase was maximal; however, there was no apparent causal relationship suggested by temporal changes in a given steroid. Variations in testosterone metabolism, by regulating the quantity and quality of active hormone in close proximity to receptor sites, may be responsible for the changes in feedback sensitivity and behavioral responsiveness that are known to occur in seasonal breeders.

Chronic morphine and testosterone treatment: effects on norepinephrine and serotonin metabolism and gonadotropin secretion in male rats

The effects of sustained-release implants of morphine (M) and/or testosterone (T) on serum gonadotropin levels and norepinephrine (NE) and serotonin (5-HT) metabolism in brain regions were examined. While 4 days of M or 5 mmol T treatment were without significant effect, the combination dramatically decreased circulating levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Castration increased NE content of the mediobasal hypothalamus (MBH), and although M, 5 mmol T, or their combination significantly reduced NE levels in the MBH, they remained elevated compared to intact or 30 mmol T-treated rats. Further, in the MBH no differences in normetanephrine (NME) levels, nor in NME:NE ratios, nor 5-HT metabolism were evident. In the preoptic area-anterior hypothalamus, NE or 5-HT metabolism were not altered by castration and M and/or T. These results show that M and T interact to suppress LH and FSH release in the apparent absence of any appreciable effect on hypothalamic monoamines.

Responses of anterior hypothalamic-preoptic thermosensitive neurons to locally applied capsaicin

The effects of local application of capsaicin on the activity of single thermosensitive neurons in the anterior hypothalamic-preoptic area were studied in the urethane-anesthetized rat. Local injection of capsaicin through a cannula to the vicinity of the neurons increased the activity in 15 of 28 warm-units, decreased the activity in 2 of 4 cold-units and had no effect on 5 of 10 thermally-insensitive units. Electrophoretic application of capsaicin with the use of multibarrelled microelectrodes excited 16 of 27 warm-units, inhibited 12 of 17 cold-units and had no effect on 35 of 60 thermally-insensitive units. Progressive decreases in the responsiveness of the neurons to both capsaicin and the hypothalamic temperature were observed with repeated applications of capsaicin. Many neurons ceased firing after showing excitatory or inhibitory responses to single or repeated applications of capsaicin either by local injection or electrophoretic application. The results may explain the acute thennolytic response, as well as the subsequent decrease in responsiveness to the injection of capsaicin into the anterior hypothalamic-preoptic area, on the basis of changes in the activity of thermosensitive neurons in the anterior hypothalamic-preoptic area.