Substance P regulates puberty onset and fertility in the female mouse

Puberty is a tightly regulated process that leads to reproductive capacity. Kiss1 neurons are crucial in this process by stimulating GnRH, yet how Kiss1 neurons are regulated remains unknown. Substance P (SP), an important neuropeptide in pain perception, induces gonadotropin release in adult mice in a kisspeptin-dependent manner. Here, we assessed whether SP, through binding to its receptor NK1R (neurokinin 1 receptor), participates in the timing of puberty onset and fertility in the mouse. We observed that 1) selective NK1R agonists induce gonadotropin release in prepubertal females; 2) the expression of Tac1 (encoding SP) and Tacr1 (NK1R) in the arcuate nucleus is maximal before puberty, suggesting increased SP tone; 3) repeated exposure to NK1R agonists prepubertally advances puberty onset; and 4) female Tac1-/- mice display delayed puberty; moreover, 5) SP deficiency leads to subfertility in females, showing fewer corpora lutea and antral follicles and leading to decreased litter size. Thus, our findings support a role for SP in the stimulation of gonadotropins before puberty, acting via Kiss1 neurons to stimulate GnRH release, and its involvement in the attainment of full reproductive capabilities in female mice. Copyright © 2015 by the Endocrine Society

Pilot study to define criteria for Pituitary Tumors Centers of Excellence (PTCOE): results of an audit of leading international centers

Purpose: The Pituitary Society established the concept and mostly qualitative parameters for defining uniform criteria for Pituitary Tumor Centers of Excellence (PTCOEs) based on expert consensus. Aim of the study was to validate those previously proposed criteria through collection and evaluation of self-reported activity of several internationally-recognized tertiary pituitary centers, thereby transforming the qualitative 2017 definition into a validated quantitative one, which could serve as the basis for future objective PTCOE accreditation. Methods: An ad hoc prepared database was distributed to nine Pituitary Centers chosen by the Project Scientific Committee and comprising Centers of worldwide repute, which agreed to provide activity information derived from registries related to the years 2018–2020 and completing the database within 60 days. The database, provided by each center and composed of Excel® spreadsheets with requested specific information on leading and supporting teams, was reviewed by two blinded referees and all 9 candidate centers satisfied the overall PTCOE definition, according to referees’ evaluations. To obtain objective numerical criteria, median values for each activity/parameter were considered as the preferred PTCOE definition target, whereas the low limit of the range was selected as the acceptable target for each respective parameter. Results: Three dedicated pituitary neurosurgeons are preferred, whereas one dedicated surgeon is acceptable. Moreover, 100 surgical procedures per center per year are preferred, while the results indicated that 50 surgeries per year are acceptable. Acute post-surgery complications, including mortality and readmission rates, should preferably be negligible or nonexistent, but acceptable criterion is a rate lower than 10% of patients with complications requiring readmission within 30 days after surgery. Four endocrinologists devoted to pituitary diseases are requested in a PTCOE and the total population of patients followed in a PTCOE should not be less than 850. It appears acceptable that at least one dedicated/expert in pituitary diseases is present in neuroradiology, pathology, and ophthalmology groups, whereas at least two expert radiation oncologists are needed. Conclusion: This is, to our knowledge, the first study to survey and evaluate the activity of a relevant number of high-volume centers in the pituitary field. This effort, internally validated by ad hoc reviewers, allowed for transformation of previously formulated theoretical criteria for the definition of a PTCOE to precise numerical definitions based on real-life evidence. The application of a derived synopsis of criteria could be used by independent bodies for accreditation of pituitary centers as PTCOEs

Standards of care for medical management of acromegaly in pituitary tumor centers of excellence (PTCOE)

Purpose: A series of consensus guidelines on medical treatment of acromegaly have been produced in the last two decades. However, little information is available on their application in clinical practice. Furthermore, international standards of acromegaly care have not been published. The aim of our study was to report current standards of care for medical therapy of acromegaly, using results collected through an audit performed to validate criteria for definition of Pituitary Tumor Centers of Excellence (PTCOE). Methods: Details of medical treatment approaches to acromegaly were voluntarily provided by nine renowned international centers that participated in this audit. For the period 2018–2020, we assessed overall number of acromegaly patients under medical treatment, distribution of patients on different treatment modalities, overall biochemical control rate with medical therapy, and specific control rates for different medical treatment options. Results: Median number of total patients and median number of new patients with acromegaly managed annually in the endocrinology units of the centers were 206 and 16.3, respectively. Median percentage of acromegaly patients on medical treatment was 48.9%. Among the patients on medical treatment, first-generation somatostatin receptor ligand (SRL) monotherapy was used with a median rate of 48.7%, followed by combination therapies with a median rate of 29.3%. Cabergoline monotherapy was used in 6.9% of patients. Pegvisomant monotherapy was used in 7 centers and pasireotide monotherapy in 5 centers, with median rates of 7.9% and 6.3%, respectively. Conclusions: Current standards of care in PTCOEs include use of first-generation SRLs as the first medical option in about 50% of patients, as recommended by consensus guidelines. However, some patients are kept on this treatment despite inadequate control suggesting that cost-effectiveness, availability, patient preference, side effects, and therapeutic inertia may play a possible role also in PTCOE. Moreover, at odds with consensus guidelines, other monotherapies for acromegaly appear to have a marginal role as compared to combination therapies as extrapolated from PTCOE practice data. Presence of uncontrolled patients in each treatment category suggest that further optimization of medical therapy, as well as use of other therapeutic tools such as radiosurgery may be needed

Thin-film plate polarizer with Fabry-Perot filter design

A thin-film plate polarizer with a polarization ratio T/Ts> 1000 for single laser wavelengths can be realized if a Fabry-Perot filter is used. The spectral width of the polarization region of the filter polarizer is smaller than that of the usual long-wave pass filter, but there are not the practical difficulties of depositing multilayer systems with a large number of layers having nonquarter-wave thicknesses. For theoretical analysis, the principle of equivalent layer is extended to the Fabry-Perot design. Experimental results of the Fabry-Perot filter polarizer for different laser wavelengths, and with different coating materials, are presented

Microstructured multilayer dielectric coatings with binary optical functions

Micropatterned interference filters have been developed by dry etching of dielectric multilayer stacks. Apart from the optical demands on the conventional filter design there are new requirements originating from the pattening process, which has to be stopped at the interface between two layers. In this paper the fundamental problems associated with the design and the development of micropatterned multilayer dielectric stacks are discussed. Details of the production of a two-stage filterarray are described and experimental results are presented

Shift-free narrowband filters for the UV-B region

Monitoring of stratospherical ozone depletion by filter rediometers calls for narrowband filters with outstanding parameters. At filter wavelengths down to 300 nm narrow bandwidth, high peak transmittance together with high out-of-band blocking especially at longer wavelength are demanded. Furthermore, filters have to be completely free of wavelength shift caused by humidity. Conventional interference filters suffer from such shift because of the water sorption of the evaporated layers. By using plasma ion assisted deposition (Advanced Plasma Source - APS, Leybold) of zirconia and silicia layers we succeeded in manufacturing blocked two-cavity filters with full width at half maximum (FWHM) of 1.7 nm and peak transmittance of 17 per cent at the center wavelength in the UV-B region. Outside the transmission band from UV to NIR (>= 1000 nm) optical density is at least 6. There was no decrease in wavelength of such filters (without hermetisation) by changing relative humidity from 100 per cent to 0 per cent. Corresponding conventional filters shifted 4.5 nm under the same conditions. The filter performance achieved allows use for the development of sensitive and specific instrumentation for environmental, climate, and meterological research

Micropatterned multilayer dielectric filters with two spectral characteristics

Micropatterned interference filters are developed by dry etching of dielectric multilayer stacks. The application of reactive-ion etching (RIE) techniques combined with the use of an etchstop layer are shown to be quite effective in producing two-stage micropatterns with defined spectral properties. By using a MgF2 underlayer the etching of TiO2 and Si02 layers is stopped exactly. Which provides the possibility to develop large area patterns (>lxl cm2) with feature sizes as small as 10 mu m. The distortion of edge features is shown to be better than 1 mu m. A filter array was developed providing high-reflection and antireflection coatings within a period of 20 mu m

Identification of gene networks modulated by activin in LßT2 cells using DNA microarray analysis

Activins, members of the TGFß family of proteins, are widely expressed in a variety of tissues. First identified based on their ability to regulate biosynthesis and secretion of follicle-stimulating hormone (FSH), activins have also been shown to modulate development, cell growth, apoptosis, and inflammation. Despite their many known functions, the precise mechanisms and downstream signaling pathways by which activins mediate their diverse effects remain unknown. We have used a DNA microarray assay to identify genes that are regulated by activin, alone or in combination with gonadotropin-releasing hormone (GnRH), another major regulator of FSH, in a murine gonadotrope-derived cell line (LßT2). We used mRNA from these cells to screen Affymetrix Mu74av2 mouse Gene Chip oligonucleotide microarrays, representing approximately 12,400 mouse genes. Treatment of LßT2 cells with activin A, a gonadotropin-releasing hormone agonist (GnRHA) or activin A plus GnRHA resulted in alterations in levels of gene expression that ranged in magnitude from 15 to 67-fold. Data analysis identified 268 transcripts that were up- or down-regulated by twofold or more. Distinct sets of genes were affected by treatment with activin, GnRHA and activin plus GnRHA, suggesting interactions between activin and GnRHA. Changes in expression of seven randomly selected representative genes identified by the microarray technique were confirmed by real-time quantitative PCR and semi-quantitative reverse transcription/PCR (RT/PCR). Modulation of expression of genes by activin suggests that activin may mediate its effects through a variety of signaling pathways

Influence of substrate cleaning on LIDT of 355 nm HR coatings

An advanced high-purity reactive e-beam evaporation process was used to deposit Al2O3/SiO2 HR coatings for 355 nm (Nd: YAG third harmonic) high-power laser applications. Both 1:1 an R:1, 6 ns pulse width, laser-induced damage threshold (LIDT) tests for normal (0 deg) and non-normal (45 deg) incident designs were performed to study the influence of quartz substrate cleaning. Damage test results indicate very high LIDT values on clean substrates. Some tested points have R:1 LIDT above 20 J/cm2. Post-cleaning of coated substrates degrades LIDT