Patterns of preoptic–hypothalamic neuronal activation and LH secretion in female sheep following the introduction and withdrawal of novel males

2019 ◽  
Vol 31 (11) ◽  
pp. 1674
Author(s):  
Penny A. R. Hawken ◽  
Jeremy T. Smith ◽  
Trina Jorre de St Jorre ◽  
Tammi Esmaili ◽  
Christopher J. Scott ◽  
...  

The neuroendocrine response of female sheep to a novel male involves neural activation in the hypothalamus. However, if males are removed, the gonadotrophic signal declines, so the neural activity is likely to change. We examined Fos-immunoreactive (IR) cells in hypothalamic tissues from seasonally anovulatory female sheep exposed to males for 2 or 6h, or for 2h followed by 4h isolation from males. Control females were killed in the absence of male exposure. Male introduction increased LH secretion in all females; male removal was associated with a reduction only in mean and basal LH concentrations. Females exposed to males for 2h had more Fos-IR cells in the arcuate nucleus (ARC), ventromedial nucleus of the hypothalamus (VMH) and organum vasculosum of the lamina terminalis (OVLT) than control females. Fos-IR cells in the preoptic area (POA) were only greater than in control females after 6h exposure to a male. Removal of males decreased the number of Fos-IR cells in the ARC, VMH and OVLT, but not in the POA. Thus, hypothalamic neural activation and LH secretion in female sheep are stimulated by males and decline after male removal. However, activation in the POA persists after removal and may explain the incomplete decline in the LH response.

Endocrinology ◽  
2012 ◽  
Vol 153 (6) ◽  
pp. 2756-2765 ◽  
Author(s):  
Casey C Nestor ◽  
Amanda M.S. Briscoe ◽  
Shay M. Davis ◽  
Miro Valent ◽  
Robert L. Goodman ◽  
...  

Puberty onset in female sheep is marked by a decrease in estradiol-negative feedback, allowing for the increase in GnRH and LH pulses that heralds the first ovulation. Based on recent genetic studies in humans, two possible neuropeptides that could promote puberty onset are kisspeptin and neurokinin B (NKB). Our first experiment determined whether the NKB agonist, senktide, could stimulate LH secretion in prepubertal ewes. A second study used prepubertal and postpubertal ewes that were intact or ovariectomized (OVX) to test the hypothesis that expression of kisspeptin and NKB in the arcuate nucleus increased postpubertally. For comparison, kisspeptin and NKB expression in age-matched intact, and castrated males were also examined. In experiment 1, the percentage of ewes showing an LH pulse immediately after injection of senktide (100 μg, 60%; 500 μg, 100%) was greater than that for water-injected controls (experiment 1a, 25%; experiment 1b, 20%). In experiment 2, kisspeptin-positive cell numbers in the arcuate nucleus increased after puberty in intact females and were increased by OVX in prepubertal but not postpubertal ewes. Changes in kisspeptin cell numbers were paralleled by changes in kisspeptin-close contacts onto GnRH neurons in the medial preoptic area. NKB cell numbers did not differ significantly between intact prepubertal and postpubertal ewes but increased with OVX in both age groups. NKB fiber immunoreactivity was greater in postpubertal than in prepubertal intact ewes. In age-matched males, kisspeptin and NKB cell numbers increased with castration, but decreased with age. These results support the hypothesis that kisspeptin is a gatekeeper to female ovine puberty and raise the possibility that NKB may also play a role, albeit through different means.


2010 ◽  
Vol 22 (9) ◽  
pp. 129
Author(s):  
C. J. Scott ◽  
C. A. Setterfield ◽  
A. Caraty ◽  
S. T. Norman

Kisspeptin (KP) plays a key role in reproductive function including the regulation of gonadotrophin releasing hormone (GnRH) and luteinising hormone (LH) secretion in many species but little is known about its role in the mare. In this study, we examined the location of KP-producing neurons in the brain of the mare, their potential interactions with GnRH neurons, and temporal changes in their expression across the oestrous cycle. Mares (n = 3/group) were killed at oestrus (just prior to ovulation), mid-dioestrus, and late dioestrus and the head was perfusion fixed with paraformaldehyde, and hypothalamus collected. Coronal sections (40 μm) were used for dual-label immuno-stained for KP & GnRH. The majority of KP-immunoreactive (-ir) neurons were located in the arcuate nucleus/median eminence (especially mid and caudal regions), and periventricular nucleus. There was a trend (P = 0.09) towards increasing numbers of KP-ir neurons across the cycle. GnRH-ir neurons, located primarily in the arcuate nucleus (especially mid arcuate), as well as the preoptic area, did not change in number across the cycle. Numerous interactions between KP and GnRH neurons were observed, primarily in the arcuate nucleus; KP fibres interacting with GnRH cell bodies, fibre-fibre interactions between KP and GnRH, and GnRH fibres interacting with KP cell bodies. Overall we found KP inputs to 32% of GnRH-ir cells, but the number of these interactions did not vary across the oestrous cycle. This study has confirmed the reciprocal innervation between KP & GnRH neurons in the mare. Although we did not detect variation in the degree across the oestrous cycle this may reflect the sample size issues inherent to equine research.


Endocrinology ◽  
2015 ◽  
Vol 156 (9) ◽  
pp. 3277-3291 ◽  
Author(s):  
Maria Cernea ◽  
Vasantha Padmanabhan ◽  
Robert L. Goodman ◽  
Lique M. Coolen ◽  
Michael N. Lehman

Prenatal testosterone (T)-treated ewes display a constellation of reproductive defects that closely mirror those seen in PCOS women, including altered hormonal feedback control of GnRH. Kisspeptin/neurokinin B/dynorphin (KNDy) neurons of the arcuate nucleus (ARC) play a key role in steroid feedback control of GnRH secretion, and prenatal T treatment in sheep causes an imbalance of KNDy peptide expression within the ARC. In the present study, we tested the hypothesis that prenatal T exposure, in addition to altering KNDy peptides, leads to changes in the morphology and synaptic inputs of this population, kisspeptin cells of the preoptic area (POA), and GnRH cells. Prenatal T treatment significantly increased the size of KNDy cell somas, whereas POA kisspeptin, GnRH, agouti-related peptide, and proopiomelanocortin neurons were each unchanged in size. Prenatal T treatment also significantly reduced the total number of synaptic inputs onto KNDy neurons and POA kisspeptin neurons; for KNDy neurons, the decrease was partly due to a decrease in KNDy-KNDy synapses, whereas KNDy inputs to POA kisspeptin cells were unaltered. Finally, prenatal T reduced the total number of inputs to GnRH cells in both the POA and medial basal hypothalamus, and this change was in part due to a decreased number of inputs from KNDy neurons. The hypertrophy of KNDy cells in prenatal T sheep resembles that seen in ARC kisspeptin cells of postmenopausal women, and together with changes in their synaptic inputs and projections to GnRH neurons, may contribute to defects in steroidal control of GnRH observed in this animal model.


Author(s):  
Ashley N Lindo ◽  
Jennifer F Thorson ◽  
Michelle N Bedenbaugh ◽  
Richard B McCosh ◽  
Justin A Lopez ◽  
...  

Abstract Mechanisms in the brain controlling secretion of gonadotropin hormones in pigs, particularly luteinizing hormone (LH), are poorly understood. Kisspeptin is a potent LH stimulant that is essential for fertility in many species, including pigs. Neurokinin B (NKB) acting through neurokinin 3 receptor (NK3R) is involved in kisspeptin-stimulated LH release, but organization of NKB and NK3R within the porcine hypothalamus is unknown. Hypothalamic tissue from ovariectomized (OVX) gilts was used to determine the distribution of immunoreactive kisspeptin, NKB, and NK3R cells in the arcuate nucleus (ARC). Almost all kisspeptin neurons coexpressed NKB in the porcine ARC. Immunostaining for NK3R was distributed throughout the preoptic area (POA) and in several hypothalamic areas including the periventricular and retrochiasmatic areas but was not detected within the ARC. There was no colocalization of NK3R with gonadotropin-releasing hormone (GnRH), but NK3R-positive fibers in the POA were in close apposition to GnRH neurons. Treating OVX gilts with the progestin altrenogest decreased LH pulse frequency and reduced mean circulating concentrations of LH compared with OVX control gilts (P < 0.01), but the number of kisspeptin and NKB cells in the ARC did not differ between treatments. The neuroanatomical arrangement of kisspeptin, NKB, and NK3R within the porcine hypothalamus confirm they are positioned to stimulate GnRH and LH secretion in gilts, though differences with other species exist. Altrenogest suppression of LH secretion in the OVX gilt does not appear to involve decreased peptide expression of kisspeptin or NKB.


Endocrinology ◽  
2009 ◽  
Vol 150 (12) ◽  
pp. 5488-5497 ◽  
Author(s):  
Kathryn Backholer ◽  
Jeremy Smith ◽  
Iain J. Clarke

Abstract To further test the hypothesis that melanocortins stimulate the reproductive axis, we treated ewes with melanocortin agonist (MTII) in the luteal phase of the estrous cycle and during seasonal anestrus. Lateral ventricular infusion of MTII (10 μg/h) during the luteal phase increased LH secretion. Retrograde neuronal tracing in the brain showed few proopiomelanocortin or kisspeptin cells in the arcuate nucleus, but more than 70% of kisspeptin cells in the dorsolateral preoptic area (POA), projecting to the ventromedial POA in which GnRH cells are located. MTII infusion (20 h) was repeated in luteal phase ewes and brains were harvested to measure gene expression of preproorexin and kisspeptin. Expression of orexin in the dorsomedial hypothalamus and kisspeptin in the POA was up-regulated by MTII treatment and Kiss1 in the arcuate nucleus was down-regulated. Seasonally anestrous ewes were progesterone primed and then treated (lateral ventricular) with MTII (10 μg/h) or vehicle for 30 h, and blood samples were collected every 2 h from 4 h before infusion until 6 h afterward to monitor acute response in terms of LH levels. A rise in basal LH levels was seen, but samples collected around the time of the predicted LH surge did not indicate that an ovulatory event occurred. We conclude that melanocortins are positive regulators of the reproductive neuroendocrine system, but treatment with melanocortins does not fully overcome seasonal acyclicity. The stimulatory effect of melanocortin in the luteal phase of the estrous cycle may be via the activation of kisspeptin cells in the POA and/or orexin cells in the dorsomedial hypothalamus.


Author(s):  
Eva K Fischer ◽  
Harmony Alvarez ◽  
Katherine M Lagerstrom ◽  
Jordan E McKinney ◽  
Randi Petrillo ◽  
...  

ABSTRACTAggressive competition for resources among juveniles is documented in many species, but the neural mechanisms regulating this behavior in young animals are poorly understood. In poison frogs, increased parental care is associated with decreased water volume of tadpole pools, resource limitation, and aggression. Indeed, the tadpoles of many poison frog species will attack, kill, and cannibalize other tadpoles. We examined the neural basis of conspecific aggression in Dyeing poison frog (Dendrobates tinctorius) tadpoles by comparing individuals that won aggressive encounters, lost aggressive encounters, or did not engage in a fight. We first compared patterns of generalized neural activity using immunohistochemical detection of phosphorylated ribosomes (pS6) as a proxy for neural activation associated with behavior. We found increased neural activity in the medial pallium and preoptic area of loser tadpoles, suggesting the amphibian homologs of the mammalian hippocampus and preoptic area may facilitate loser-associated behaviors. Nonapeptides (arginine vasotocin and mesotocin) and dopamine have been linked to aggression in other vertebrates and are located in the preoptic area. We next examined neural activity specifically in nonapeptide- and tyrosine-hydroxylase-positive cells using double-label immunohistochemistry. We found increased neural activity specifically in the preoptic area nonapeptide neurons of winners, whereas we found no differences in activity of dopaminergic cells among behavioral groups. Our findings suggest the neural correlates of aggression in poison frog tadpoles are similar to neural mechanisms mediating aggression in adults and juveniles of other vertebrate taxa.


Endocrinology ◽  
2000 ◽  
Vol 141 (8) ◽  
pp. 2951-2962 ◽  
Author(s):  
Christopher J. Scott ◽  
Alan J. Tilbrook ◽  
Donna M. Simmons ◽  
John A. Rawson ◽  
Simon Chu ◽  
...  

We have used in situ hybridization to compare the distributions of estrogen receptor α (ERα) and ERβ messenger RNA (mRNA)-containing cells in the preoptic area and hypothalamus of ewes and rams. Perfusion-fixed brain tissue was collected from luteal phase ewes and intact rams (n = 4) during the breeding season. Matched pairs of sections were hybridized with sheep-specific, 35S-labeled riboprobes, and semiquantitative image analysis was performed on emulsion-dipped slides. A number of sex differences were observed, with females having a greater density of labeled cells than males (P < 0.001) and a greater number of silver grains per cell (P < 0.01) in the ventromedial nucleus for both ER subtypes. In addition, in the retrochiasmatic area, males had a greater (P < 0.05) cell density for ERα mRNA-containing cells than females, whereas in the paraventricular nucleus, females had a greater density (P < 0.05) of ERα mRNA-containing cells than males. There was a trend (P = 0.068) in the arcuate nucleus for males to have a greater number of silver grains per cell labeled for ERα mRNA. In both sexes, there was considerable overlap in the distributions of ERα and ERβ mRNA-containing cells, but the density of labeled cells within each nucleus differed in a number of instances. Nuclei that contained a higher (P < 0.001) density of ERα than ERβ mRNA-containing cells included the preoptic area, bed nucleus of the stria terminalis, and ventromedial nucleus, whereas the subfornical organ (P < 0.001), paraventricular nucleus (males only, P < 0.05), and retrochiasmatic nucleus (females only, P < 0.05) had a greater density of ERα than ERβ mRNA-containing cells. The anterior hypothalamic area and supraoptic nucleus had similar densities of cells containing both ER subtypes. The lateral septum and arcuate nucleus contained only ERα, whereas only ERβ mRNA-containing cells were seen in the zona incerta. The sex differences in the populations of ER mRNA-containing cells in the ventromedial and arcuate nuclei may explain in part the sex differences in the neuroendocrine and behavioral responses to localized estrogen treatment in these nuclei. Within sexes, the differences between the distributions of ERα and ERβ mRNA-containing cells may reflect differential regulation of the actions of estrogen in the sheep hypothalamus. Low levels of ERβ mRNA in the preoptic area and ventromedial and arcuate nuclei, regions known to be important for the regulation of reproduction, suggest that ERβ may not be involved in these functions.


Sign in / Sign up

Export Citation Format

Share Document