Lack of evidence for functional luteinising hormone chorionic gonadotropin receptors in non-pregnant human endometrial stromal cells

The human luteinising hormone chorionic gonadotropin receptor (LHCGR) is a G-protein coupled receptor activated by both human chorionic gonadotropin (hCG) and luteinizing hormone (LH), two structurally related gonadotropins with essential roles in ovulation and maintenance of the corpus luteum. LHCGR expression predominates in ovarian tissues where it elicits functional responses through cyclic adenosine mononucleotide (cAMP), Ca2+ and extracellular signal-regulated kinase (ERK) signalling. LHCGR has also been localized to the human endometrium, with purported roles in decidualization and implantation. However, these observations are contentious. In this investigation, transcripts encoding LHCGR were undetectable in bulk RNA sequencing datasets from whole cycling endometrial tissue and cultured human endometrial stromal cells (EnSC). However, analysis of single-cell RNA sequencing data revealed cell-to-cell transcriptional heterogeneity and identified a small subpopulation of stromal cells with discernible LHCGR transcripts. In HEK-293 cells expressing recombinant LHCGR, both hCG and LH elicited robust cAMP, Ca2+ and ERK signals that were absent in wild type HEK-293 cells. However, none of these responses were recapitulated in primary EnSC cultures. In addition, proliferation, viability and decidual transformation of EnSC were refractory to both hCG and LH, irrespective of treatment to induce differentiation. Although we challenge the assertion that LHCGR is expressed at a functionally active level in the human endometrium, the discovery of a discrete subpopulation of EnSC that express LHCGR transcripts may plausibly account for the conflicting evidence in the literature.

Pituitary and ovarian hormones: is their plasma concentration affected by litter size in primiparous lactating rabbit does?

Genetic selection in commercial rabbit lines based on litter size has positively improved the number of kits suckling, presumably to weaning. Although it has been proven that the energetic balance of primiparous does is due to the need to satisfy pregnancy, lactation and growth requirements, litter size adjustment from 7 to 12 kits is applied as a routine in commercial rabbit farms. The suckling stimulus provokes a prolactin (PRL) secretion, which in turn can modulate the preovulatory release of luteinising hormone (LH) and, consequently, the ovulatory and productive responses of the does. This study aimed to determine if litter size of prolific primiparous rabbit does during lactation [Group HL, with high litter density (10-12 kits; n=21) and Group LL, with low litter density (7-9 kits; n=29)] influences plasma concentration of PRL. Blood samples from lactating does were taken weekly throughout lactation starting on day 4 post-partum, until day 32 post-partum, before and immediately after suckling. In addition, the does were re-inseminated after weaning (day 32 post-partum), and sampled at 0 and 60 min after induction of ovulation to determine whether litter size affected the peak of LH, progesterone (P4) concentrations and the main productive parameters of their second pregnancy. All hormones were determined by enzyme immunoassay. Statistical analysis of the results revealed that the PRL concentrations of hyperprolific rabbit does before and immediately after a suckling stimulus from 7-9 or 10-12 kits were significanltly different, as we only detected basal levels, with a rise after weaning in both groups. More studies are necessary, delaying blood sampling to later periods of time after the suckling stimulus, in order to conclude whether the peak release of this hormone is altered or not. There were also no differences in plasma LH and progesterone levels after artificial insemination, or in productive performance of these females after their second pregnancy. In conclusion, the litter size adjustment of prolific primiparous rabbits with 7 to 12 kits determines adequate pituitary, ovarian and reproductive responses at second parturition if the does are inseminated after weaning.

Luteinising hormone-based protocol versus traditional flexible gonadotropin-releasing hormone antagonist protocol in women with normal ovarian response: study protocol for a non-inferiority trial

IntroductionMany patients demonstrate an insufficient endogenous luteinising hormone (LH) concentration during ovarian stimulation. With traditional fixed or flexible gonadotropin-releasing hormone (GnRH) antagonist protocols, antagonist administration may further reduce LH activity. Previously, we proved that LH can be used as an indicator for the timing and dosage of antagonist. Patients with a persistently low LH concentration during ovarian stimulation may not require antagonists, whereas antagonist administration can affect reproductive outcomes. To further explore this hypothesis, we designed a randomised clinical trial to compare the LH-based flexible GnRH antagonist protocol with traditional flexible GnRH antagonist protocol in women with normal ovarian response.Methods and analysisThis study was a multicentre, parallel, prospective, randomised, non-inferiority study. The primary efficacy endpoint was cumulative ongoing pregnancy rate per cycle. The study aimed to prove the non-inferiority of cumulative ongoing pregnancy rate per cycle with an LH-based flexible GnRH antagonist protocol versus traditional flexible GnRH antagonist protocol. Secondary endpoints were the high-quality embryo rate, clinical pregnancy rate and cancellation rate. Differences in cost-effectiveness and adverse events were evaluated. The cumulative ongoing pregnancy rate per cycle in women with normal ovarian response was 70%. Considering that a non-inferiority threshold should retain 80% of the clinical effect of a control treatment, a minimal clinical difference of 14% (one-sided: α, 2.5%; β, 20%) and a total of 338 patients were needed. Anticipating a 10% drop-out rate, the total number of patients required was 372.Ethics and disseminationThis trial has been approved by the Institutional Ethical Committee of Beijing Chao-Yang hospital. All participants in the trial will provide written informed consent. The study will be conducted according to the principles outlined in the Declaration of Helsinki and its amendments. Results of this study will be disseminated in peer-reviewed scientific journals.Trial registration numberChiCTR1800018077.

Mistaken administration of a repeat loading dose of Degarelix leading to acute psychosis

Lesson Advanced and metastatic prostate cancer is often managed with hormonal blockage. Luteinising hormone-releasing hormone antagonists achieve rapid testosterone suppression and are used for the treatment of advanced or metastatic prostate cancer. Degarelix is a luteinising hormone-releasing hormone antagonist and is given as a loading dose, followed by a monthly maintenance dose. We report a case where a patient was inadvertently given a second loading dose of Degarelix that resulted in acute psychosis in the form of panic attacks, delusions, suicidal thoughts, insomnia and some visual hallucinations, which are not reported as side-effects of Degarelix.

Long-term effect of neutering on plasma luteinising hormone concentration in cats

Objectives The objectives of this study were to validate a commercially available luteinising hormone (LH) cat ELISA, to determine whether the increases in plasma LH concentration that occur after neutering are maintained throughout cats’ lives and if other factors such as calendar seasons in both intact and neutered cats, and neutering age in neutered cats, influence plasma LH concentrations. Methods Stored plasma samples from client-owned cats were used for the measurement of LH concentrations. Clinical data, including age, sex, age at neutering and medical history, were reviewed. Two populations were included in this study: (1) a senior and geriatric cat population (⩾9 years old), including 18 intact and 18 neutered cats matched for age, sex and month of sample collection; and (2) an adult cat population (2–8 years old), including 45 neutered cats. LH concentrations were measured using a commercially available feline ELISA. Results Senior and geriatric neutered cats had higher plasma LH concentrations than age-matched intact cats ( P <0.001). Calendar season did not influence plasma LH concentrations in the adult ( P = 0.727) or senior/geriatric ( P = 0.745) cats included in this study. No influence of age at neutering was observed on plasma LH concentrations ( P = 0.296). Conclusions and relevance Neutering causes a significant long-term increase in LH concentrations in cats and further studies are required to determine the consequences on feline health.

Dermatological manifestation of metastatic prostate cancer

A 59-year-old man presented to the urology department with increased urinary urgency, frequency, poor urinary flow and unintentional weight loss. He had a 25-year history of idiopathic urticaria episodes which had increased in frequency over the previous 2 months. On investigation, he was found to have a raised prostate-specific antigen level. He was investigated further with a multiparametric MRI, a local anaesthetic transperineal prostate biopsy, a CT scan of chest/abdomen/pelvis with contrast and a nuclear medicine bone scan. He was diagnosed with metastatic adenocarcinoma of the prostate and commenced on a luteinising hormone-releasing hormone antagonist and referred to oncology for further treatment. Since starting treatment, he has experienced no further episodes of urticaria.