Background/Objectives: Benign prostatic hyperplasia (BPH) is a common age-related disorder in elderly men and a major cause of lower urinary tract symptoms. Lycopus lucidus Turcz. ex Benth. has been traditionally used in East Asian medicine, but its effects on BPH have not been investigated. This study evaluated the effects of L. lucidus extract (LLE) on testosterone propionate (TP)-induced BPH in rats and explored associated changes in androgen metabolism. Methods: Male Sprague-Dawley rats were orchiectomized except for the sham group and injected with TP (3 mg/kg, s.c.) for 28 days. During TP exposure, rats received oral LLE (100 or 200 mg/kg/day), finasteride (1 mg/kg/day), or vehicle. Prostate weight, prostate index, and histological changes in the ventral prostate were evaluated. Serum testosterone and dihydrotestosterone levels were measured using an enzyme-linked immunosorbent assay. The protein expression of 5α-reductase type 2, aromatase, Bax, and Bcl-2 in the ventral prostate tissue was analyzed by Western blotting. Results: LLE (200 mg/kg) significantly reduced prostate weight and prostate index and improved histological alterations, comparable to finasteride. LLE increased serum testosterone levels and decreased the dihydrotestosterone/testosterone ratio. Expression of 5α-reductase type 2 and aromatase in the ventral prostate tissue was significantly downregulated, while Bax and Bcl-2 expression and the Bax/Bcl-2 ratio remained unchanged. Conclusions: LLE attenuated TP-induced prostatic hyperplasia in rats, suggesting that modulation of androgen metabolism may contribute to its anti-hyperplastic effects. These findings support further investigation of L. lucidus extract in BPH.

Androgenetic alopecia (AGA) is the most common form of hair loss, with a high prevalence worldwide. In this study, we aimed to investigate the potential of Tenebrio molitor larva trypsin hydrolysate (TMTH), an insect-derived bioactive hydrolysate, as a functional ingredient candidate for AGA. In vitro and in vivo assessments demonstrated that TMTH promoted human hair dermal papilla (HDP) cell proliferation, restored β-catenin expression, and alleviated dihydrotestosterone (DHT)-induced inhibition. In a testosterone propionate (TP)-induced alopecia mouse model, oral TMTH administration increased hair coverage and follicle number, upregulated Wnt/β-catenin and PI3K/Akt signaling, reduced androgen receptor expression, enhanced antioxidant-related responses, and suppressed inflammatory markers. These findings suggest that TMTH may ameliorate AGA-related phenotypes by modulating hair growth-related signaling, local androgen-related responses, oxidative stress, and inflammation, thereby supporting its potential as a functional ingredient candidate for hair loss management.

Diffuse alveolar hemorrhage (DAH) is a lethal, female-biased complication of systemic lupus erythematosus (SLE). While adaptive immunity is a known driver, the role of innate lymphoid cells (ILCs) in DAH and the contribution of sex hormones to this process remain unclear. To characterize pulmonary ILC remodeling during DAH and evaluate whether androgen signaling modulates natural killer (NK) cell homeostasis and disease severity. A pristane-induced DAH model was established in C57BL/6J and Rag2 [-/-] mice. Pulmonary ILCs were profiled by single-cell transcriptomics and flow cytometry. Baseline sex differences were compared between healthy humans and mice. In vivo interventions included male castration, female testosterone propionate (TP) administration, and antibody-mediated NK cell depletion. DAH was accompanied by a marked reduction in pulmonary NK cell frequency in both C57BL/6J and Rag2 [-/-] mice, indicating an innate feature independent of adaptive lymphocytes. DAH-associated NK cells displayed an activated but constrained state, showing increased expression of effector-associated genes Prf1 and Ifng, together with the inhibitory receptor gene Lag3. At baseline, healthy human females and female mice exhibited lower NK cell frequencies than males. While male castration did not significantly alter DAH severity, TP administration in females restored pulmonary NK cell dominance and significantly attenuated disease severity. NK cell depletion prior to challenge led to a trend toward more severe hemorrhage (p = 0.084). Pulmonary NK cells are reduced in a lupus-associated DAH model and may participate in disease development. Androgen treatment restores pulmonary NK cell predominance and attenuates DAH severity, supporting further investigation of strategies aimed at restoring or preserving pulmonary NK cell homeostasis and function as potential therapeutic approaches for DAH.

Rana dybowskii is an economically important amphibian in Northeast China, valued for its medicinal oviduct (Oviductus Ranae). However, the low proportion of females in artificial culture severely restricts industrial productivity. To elucidate the molecular mechanisms of hormone-induced sex reversal, based on our previous research results, we exposed tadpoles to 17β-estradiol (E2) or testosterone propionate (TP). We then monitored gonadal histology, conducted multi-stage transcriptome sequencing, and validated key genes via qRT-PCR. The results show that induction treatment with 40 μg·L[-1] E2 and 80 μg·L[-1] TP resulted in 93.33% female and 100% male populations, respectively. Both hormones promoted germ cell proliferation at the undifferentiated stage and directed stable ovarian or testicular development without intersex abnormalities. Ovarian differentiation involved progressive multi-wave transcriptional reprogramming, whereas testicular differentiation exhibited a concentrated gene expression burst during gonadal maturation. Steroid hormone biosynthesis, Wnt, and PPAR pathways formed the core regulatory network. Three female-biased genes (3α-hsd, Adcy3, Rspo1) and three male-biased genes (Ptgs2, Sox9, Shbg) were identified, with their expression dynamics aligned with histological progression. This study defines the optimal parameters and molecular signatures of bidirectional sex reversal in R. dybowskii. It provides a practical foundation for sex-control breeding and offers amphibian-based evidence for the conservation and plasticity of vertebrate sex determination.

The current study examines the role of testosterone and androgen deprivation in regulating mitochondrial quality control, autophagy, and apoptosis during CCl4-induced chronic liver injury. Male rats were allocated to Sham, CCl4, TP + CCl4 (testosterone-treated), and Cas + CCl4 (castrated) groups for 4, 8, and 12 weeks, validated through in vitro assays. Mitochondrial function (MitoTracker, MFN2), lysosomal integrity (LAMP1), autophagy markers (LC3B, Beclin-1, p62/SQSTM1), apoptosis regulators (Bcl-2, cleaved caspase-3), and mTOR signaling were assessed by qRT-PCR, immunohistochemistry, and immunofluorescence. CCl4 exposure caused progressive increases in cellular stress and fibrotic markers (α-SMA, TGF-β1, and TXNIP), progressive mitochondrial dysfunction, impaired mitochondrial-lysosomal coordination, reduced Beclin-1 and LC3B, p62 accumulation, and a shift toward an anti-apoptotic Bcl-2 imbalance. Testosterone treatment restored mitochondrial membrane potential in vitro, normalized MitoTracker and MFN2 expression, preserved LAMP1 levels, and partially sustained mitochondrial-lysosomal coupling. TP also enhanced Beclin-1 and LC3B, reduced p62 accumulation, and sustained mTOR activity, consistent with improved autophagic flux. Moreover, TP-lowered Bcl-2 was associated with controlled cleaved caspase-3 activation, suggesting selective clearance of damaged hepatocytes rather than widespread apoptosis. In contrast, Cas + CCl4 animals showed exaggerated mitochondrial impairment, persistent p62 accumulation, reduced LC3B and mTOR signaling, and a pro-apoptotic cleaved caspase-3 profile. Together, these findings demonstrate that testosterone supports mitochondrial-lysosomal homeostasis and autophagy during toxic liver injury, whereas androgen deprivation favors defective autophagy and maladaptive apoptosis, underscoring hormone-dependent regulation of hepatocellular stress responses.

Persistent microinflammation in androgenetic alopecia (AGA) may contribute to hair follicle miniaturization, but whether scalp microbial dysbiosis serves as its trigger remains unclear. This study integrated clinical samples, an animal model, and in vitro experiments to investigate the scalp microbiome in AGA.

Empathetic responses, including socially-transferred pain hypersensitivity (STPH) and the targeted caring behaviors shown as allolicking (injury site targeted licking) and allogrooming (body grooming) toward a familiar demonstrator with pain, can be quantified in rodents using a dyadic social interaction (DSI) paradigm. These responses exhibit sex differences. Although our prior research established that β-estradiol is selectively required for allolicking, but not allogrooming in female mice, the overall scope of sex hormones remains unclear. Here, we discovered androgen deficiency following bilateral orchiectomy (ORC) in male observers impaired engagement of allolicking and allogrooming, STPH and social sniffing, but not self-grooming towards a familiar demonstrator. A 7-day replacement therapy with testosterone propionate (TP; 0.5, 1.0, 2.0 mg/kg bw, s.c.) prevented these deficits, but β-estradiol (E2; 0.5, 1.0, 2.0 mg/day, s.c.) failed. Moreover, E2 administration significantly suppressed both allolicking and allogrooming in intact male observers. In intact female observers, TP selectively enhanced both sniffing and allogrooming in terms of time and bouts, however, it suppressed the bouts of allolicking although the total time of allolicking remained unchanged. TP had no effects on STPH or self-grooming in intact female observers. Thus, we demonstrate that testosterone is essential for sniffing, allolicking and allogrooming behaviors in male and allogrooming (but not allolicking) in intact female, while estrogen inhibits empathetic behaviors in intact male. This fundamental sexual dimorphism in hormonal regulation offers promising insights for developing sex-specific hormone therapies following gonadectomy.

Validated techniques for androgen replacement in swine research models are limited, particularly for studies requiring controlled hormone delivery in males during early development. We adapted a silicone-based androgen implant methodology originally developed for adult female pigs to establish an androgen replacement model in castrated juvenile male pigs.•Castrated male pigs were surgically implanted with low (0.5 g), medium (1.0 g), or high (2.0 g) doses of testosterone propionate (TP), and compared with castrated controls.•Intact male pigs were included as a physiologically relevant reference group to benchmark implant-derived testosterone concentrations against endogenous androgen production during juvenile development.•Circulating testosterone was monitored weekly for 49 days to evaluate the concentration and duration of testosterone release.•Body weights were recorded weekly to assess body weight gain.Testosterone propionate implants produced a dose-dependent elevation in circulating testosterone that peaked between 7 and ​14 days post-implantation and reached or exceeded concentrations of intact males. Following peak release, testosterone levels gradually declined across all implant groups but remained elevated relative to castrated controls throughout the 49-day study period, with the medium- and high-dose groups maintaining the highest concentrations. Growth rates of animals were similar across experimental groups, indicating that TP implantation did not adversely affect overall growth during the study. These findings validate silicone-based TP surgical implants as a reliable method for sustained androgen delivery in juvenile, prepubertal pigs, establishing a tractable model for mechanistic studies of androgen action with translational relevance to human and animal health.