Melanin-concentrating hormone in the medial preoptic area reduces active components of maternal behavior in rats

Melanin-concentrating hormone (MCH) is an inhibitory neuropeptide mainly synthesized in neurons of the lateral hypothalamus and incerto-hypothalamic area of mammals that has been implicated in behavioral functions related to motivation. During lactation, this neuropeptide is also expressed in the medial preoptic area (mPOA), a key region of the maternal behavior circuitry. Notably, whereas MCH expression in the mPOA progressively increases during lactation, maternal behavior naturally declines, suggesting that elevated MCHergic activity in the mPOA inhibit maternal behavior in the late postpartum period. To explore this idea, we assessed the maternal behavior of early postpartum females following bilateral microinfusions of either MCH (50 and 100 ng/0.2 μl/side) or the same volume of vehicle into the mPOA. As expected, females receiving 100 ng MCH into the mPOA exhibited significant deficits in the active components of maternal behavior, including retrieving and nest building. In contrast, nursing, as well as other behaviors, including locomotor activity, exploration, and anxiety-like behavior, were not affected by intra-mPOA MCH infusion. The present results, together with previous findings showing elevated expression of this neuropeptide toward the end of the postpartum period, suggest that modulation of mPOA function by MCH may contribute to the weaning of maternal responsiveness characteristic of the late postpartum period.     

Rapid in vitro micropropagation of Agapanthus praecox

In vitro micropropagation and acclimatization for the ornamental Agapanthus praecox, are reported. The influence of different growth regulators on shoot multiplication from shoot-tip explants of A. praecox was investigated. Prolific shoot multiplication (47.3 ± 1.96 shoots per explant) was achieved on Murashige and Skoog (MS) medium supplemented with 22.2 μM benzyladenine (BA), 2.9 μM indole-3-acetic acid (IAA), and 4.5 μM thidiazuron (TDZ). Shoots were rooted on half-strength MS basal medium supplemented with 5.7 μM IAA and 2.5 μM 2-isopentenyladenine (2iP) with 11.3 ± 0.78 roots per shoot. The in vitro-raised plants were established successfully in a 1:1 (v/v) vermiculite:sand mixture when maintained in a greenhouse with 100% survival. The elongated shoots (more than 5 cm in length) were treated for rooting and acclimatization in a moistened (5.7 μM IAA and 2.5 μM 2iP) vermiculite:sand (1:1 v/v) mixture, first in the misthouse and then in the greenhouse. Rooting and acclimatization was achieved simultaneously (100%) in the misthouse which was followed by greenhouse cultivation. This system can be used for rapid mass clonal propagation of A. praecox, for conservation strategies, commercial production, gene transformation studies and to produce phytomedicines.     

New triterpene saponins from the seed cake of Camellia Oleifera and their cytotoxic activity

Two new oleanane-type triterpene saponins, identified as 16α-hydroxy-22-O-angeloyl-23-formyl-28,31-dihydroxymethylene-olean-12-ene-3β-O-{β-d-galactopyranosyl-(1 → 2)[β-d-xylopyranosyl-(1 → 2)-α-l-arabinopyranosyl(1 → 3)]-β-d-glucopyranosiduronic acid} (oleiferasaponin B₁, 1) and 22-O-hydrocinnamoyl-23-formyl-28-dihydroxymethylene-olean-12-ene-3β-O-{β-d-glucopyranosyl-(1 → 2)[β-d-xylopyranosyl-(1 → 2)-α-l-arabinopyranosyl(1 → 3)]-β-d-glucopyranosiduronic acid} (oleiferasaponin B₂, 2), were isolated from the seed cake of Camellia oleifera Abel. Their structures were established by extensive 1D- and 2D-NMR experiments along with TOF-MS analysis and acid hydrolysis. The cytotoxicity of the isolated compounds was evaluated in four human carcinoma cell lines: A 549, SK-OV-3, SK-MEL-2 and HCT15. Both compounds 1 and 2 exhibited significantly cytotoxic activity with IC₅₀ values of 18.5 μM (A549), 11.3 μM (SK-OV-3), 13.9 μM (SK-MEL-2) and 1.6 μM (HCT15) for 1 and IC₅₀ values of 8.4 μM (A549), 6.3 μM (SK-OV-3), 9.2 μM (SK-MEL-2) and 0.8 μM (HCT15) for 2. In addition, compound 2 showed more effective cytotoxic activity than compound 1.     

Effect of mercury and gold on growth,nutrient uptake,and anatomical changes in Chilopsis linearis

Plants of Chilopsis linearis were grown with 0, 50, 100, and 200 μM Hg [as Hg(CH₃COO)₂] and 0 and 50 μM Au (as KAuCl₄) in hydroponics. The results showed that seedling grown with 50 μM Au + 50 μM Hg and 50 μM Au + 100 μM Hg had roots 25 and 55% shorter than control roots, respectively. The element uptake determination using ICP/OES demonstrated that Hg at 50 and 100 μM (with and without Au) significantly increased (p < 0.05) the S concentration in leaves. On the other hand, the concentration of Fe significantly increased in roots of plants treated with Au–Hg. In addition, the stems of plants treated with Hg at 100 μM, with and without Au, had 239 and 876 mg Hg/kg dry biomass (d wt), respectively. Also, at 50 μM Hg, with and without Au, stems accumulated 375 and 475 mg Hg/kg d wt. The Hg concentration in leaves (287 mg Hg/kg d wt) was higher (p < 0.05) for the treatment containing 50 μM Au + 100 μM Hg. Without Au, the Hg concentration in leaves decreased to 75 mg Hg/kg d wt. Toxicity symptoms induced by Hg in cortex cells and the vascular system were lower in plants exposed to 50 μM Au + 50 μM Hg compared to plants exposed to 50 μM Hg only. Further, the SEM micrographs revealed deposition of Au–Hg particles inside the root. Although the concentrations of Hg used in this study showed different degree of toxicity, the plants displayed good agronomic value.     

Pharmacological characterization of the mechanisms involved in the vasorelaxation induced by progesterone and 17β-estradiol on isolated canine basilar and internal carotid arteries

Progesterone and 17β-estradiol induce vasorelaxation through non-genomic mechanisms in several isolated blood vessels; however, no study has systematically evaluated the mechanisms involved in the relaxation induced by 17β-estradiol and progesterone in the canine basilar and internal carotid arteries that play a key role in cerebral circulation. Thus, relaxant effects of progesterone and 17β-estradiol on KCl- and/or PGF_2α-pre-contracted arterial rings were investigated in absence or presence of several antagonists/inhibitors/blockers; the effect on the contractile responses to CaCl₂ was also determined. In both arteries progesterone (5.6–180 μM) and 17β-estradiol (1.8–180 μM): (1) produced concentration-dependent relaxations of KCl- or PGF_2α-pre-contracted arterial rings; (2) the relaxations were unaffected by actinomycin D (10 μM), cycloheximide (10 μM), SQ 22,536 (100 μM) or ODQ (30 μM), potassium channel blockers and ICI 182,780 (only for 17β-estradiol). In the basilar artery the vasorelaxation induced by 17β-estradiol was slightly blocked by tetraethylammonium (10 mM) and glibenclamide (K_ATP; 10 μM). In both arteries, progesterone (10–100 μM), 17β-estradiol (3.1–31 μM) and nifedipine (0.01–1 μM) produced a concentration-dependent blockade of the contraction to CaCl₂ (10 μM–10 mM). These results suggest that progesterone and 17β-estradiol produced relaxation in the basilar and internal carotid arteries by blockade of L-type voltage dependent Ca²⁺ channel but not by genomic mechanisms or production of cAMP/cGMP. Potassium channels did not play a role in the relaxation to progesterone in both arteries or in the effect of 17β-estradiol in the internal carotid artery; meanwhile K_ATP channels play a minor role on the effect of 17β-estradiol in the basilar artery.     

Potent and selective HIV-1 ribonuclease H inhibitors based on a 1-hydroxy-1,8-naphthyridin-2(1H)-one scaffold

Optimization studies using an HIV RNase H active site inhibitor containing a 1-hydroxy-1,8-naphthyridin-2(1H)-one core identified 4-position substituents that provided several potent and selective inhibitors. The best compound was potent and selective in biochemical assays (IC₅₀ = 0.045 μM, HIV RT RNase H; 13 μM, HIV RT-polymerase; 24 μM, HIV integrase) and showed antiviral efficacy in a single-cycle viral replication assay in P4-2 cells (IC₅₀ = 0.19 μM) with a modest window with respect to cytotoxicity (CC₅₀ = 3.3 μM).     

An in vitro evaluation of epigallocatechin gallate (eGCG) as a biocompatible inhibitor of ricin toxin

The catechin, epigallocatechin gallate (eGCG), found in green tea, has inhibitory activity against a number of protein toxins and was investigated in relation to its impact upon ricin toxin (RT) in vitro. The IC₅₀ for RT was 0.08 ± 0.004 ng/mL whereas the IC₅₀ for RT + 100 μM eGCG was 3.02 ± 0.572 ng/mL, indicating that eGCG mediated a significant (p < 0.0001) reduction in ricin toxicity. This experiment was repeated in the human macrophage cell line THP-1 and IC₅₀ values were obtained for RT (0.54 ± 0.024 ng/mL) and RT + 100 μM eGCG (0.68 ± 0.235 ng/mL) again using 100 μM eGCG and was significant (p = 0.0013). The documented reduction in ricin toxicity mediated by eGCG was found to be eGCG concentration dependent, with 80 and 100 μg/mL (i.e. 178 and 223 μM respectively) of eGCG mediating a significant (p = 0.0472 and 0.0232) reduction in ricin toxicity at 20 and 4 ng/ml of RT in Vero and THP-1 cells (respectively). When viability was measured in THP-1 cells by propidium iodide exclusion (as opposed to the MTT assays used previously) 10 ng/mL and 5 ng/mL of RT was used. The addition of 1000 μM and 100 μM eGCG mediated a significant (p = 0.0015 and < 0.0001 respectively) reduction in ricin toxicity relative to an identical concentration of ricin with 1 μg eGCG. Further, eGCG (100 μM) was found to reduce the binding of RT B chain to lactose-conjugated Sepharose as well as significantly (p = 0.0039) reduce the uptake of RT B chain in Vero cells. This data suggests that eGCG may provide a starting point to refine biocompatible substances that can reduce the lethality of ricin.     

Design,modification and 3D QSAR studies of novel naphthalin-containing pyrazoline derivatives with/without thiourea skeleton as anticancer agents

Two series of novel naphthalin-containing pyrazoline derivatives C1–C14 and D1–D14 have been synthesized and evaluated for their EGFR/HER-2 inhibitory and anti-proliferation activities. Compound D14 displayed the most potent activity against EGFR and A549 cell line (IC₅₀ = 0.05 μM and GI₅₀ = 0.11 μM), being comparable with the positive control Erlotinib (IC₅₀ = 0.03 μM and GI₅₀ = 0.03 μM) and more potent than our previous compounds C0–A (IC₅₀ = 5.31 μM and GI₅₀ = 33.47 μM) and C0–B (IC₅₀ = 0.09 μM and GI₅₀ = 0.34 μM). Meanwhile, compound C14 displayed the most potent activity against HER-2 and MCF-7 cell line (IC₅₀ = 0.88 μM and GI₅₀ = 0.35 μM), being a little less potent than Erlotinib (IC₅₀ = 0.16 μM and GI₅₀ = 0.08 μM) but far more potent than C0–A (IC₅₀ = 6.58 μM and GI₅₀ = 27.62 μM) and C0–B (IC₅₀ = 2.77 μM and GI₅₀ = 3.79 μM). The docking simulation was performed to analyze the probable binding models and the QSAR models were built for reasonable design of EGFR/HER-2 inhibitors at present and in future. The structural modification of introducing naphthalin moiety reinforced the combination of our compounds and the receptor, resulting in progress of bioactivity. Moreover, the replacement of thiourea skeleton by using benzene ring resulted in the slight diversity of the two series towards specific targets.     

Isatin based Schiff bases as inhibitors of α-glucosidase: Synthesis,characterization, in vitro evaluation and molecular docking studies

Isatin base Schiff bases (1–20) were synthesized, characterized by ¹H NMR and EI/MS and evaluated for α-glucosidase inhibitory potential. Out of these twenty (20) compounds only six analogs showed potent α-glucosidase inhibitory potential with IC₅₀ value ranging in between 2.2 ± 0.25 and 83.5 ± 1.0 μM when compared with the standard acarbose (IC₅₀ = 840 ± 1.73 μM). Among the series compound 2 having IC₅₀ value (18.3 ± 0.56 μM), 9 (83.5 ± 1.0 μM), 11 (3.3 ± 0.25 μM), 12 (2.2 ± 0.25 μM), 14 (11.8 ± 0.15 μM), and 20 (3.0 ± 0.15 μM) showed excellent inhibitory potential many fold better than the standard acarbose. The binding interactions of these active analogs were confirmed through molecular docking.     

Difficulties with emotion regulation moderate the association between childhood history of maltreatment and cortisol reactivity to psychosocial challenge in postpartum women

Exposure to child maltreatment can lead to long-term emotional difficulties and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. However, no prior work has examined emotion regulation as a moderator of the association between childhood history of maltreatment and cortisol response to psychosocial challenge. Amongst a sample of 140 postpartum women, associations between childhood maltreatment, emotion regulation, and cortisol response to a computerized Emotional Stroop paradigm were examined using structural equation modeling. Three saliva samples (baseline, 20- and 40-min post-challenge) were collected and later assayed for cortisol. Stepwise regression analyses revealed that difficulties with emotion regulation significantly moderated the association between maternal history of child maltreatment and cortisol reactivity (β = − 0.17, CI_.95 = − 0.31, − 0.04, t = − 2.51, p = 0.01). Specifically, women with higher child maltreatment scores and greater difficulties with emotion regulation displayed reduced cortisol reactivity. This finding suggests that diminished emotion regulation capacity may uniquely contribute to blunted physiological reactivity in postpartum women exposed to higher levels of child maltreatment. As the postpartum period has significant implications for maternal well-being and infant development, these findings are discussed in terms of adaptive responsivity, maternal behaviour, and clinical practice.     

Design,synthesis and biological evaluation of 3-benzyloxy-linked pyrimidinylphenylamine derivatives as potent HIV-1 NNRTIs

A novel series of 3-benzyloxy-linked pyrimidinylphenylamine derivatives (8a–8s) was designed, synthesized and evaluated for their in vitro anti-HIV activity in MT-4 cell cultures. Most of the compounds inhibited wild-type (wt) HIV-1 replication in the lower micromolar concentration range (EC₅₀ = 0.05–35 μM) with high selectivity index (SI) values (ranged from 10 to >4870). In particular, 8h and 8g displayed excellent antiretroviral activity against wt HIV-1 with low cytotoxicity (EC₅₀ = 0.07 μM, CC₅₀ >347 μM, SI >4870; EC₅₀ = 0.05 μM, CC₅₀ = 42 μM, SI = 777, respectively), comparable to that of the marked drug nevirapine (EC₅₀ = 0.113 μM, CC₅₀ >15 μM, SI >133). In order to confirm the binding target, 8h was selected to perform the anti-HIV-1 RT assay. Additionally, preliminary structure activity relationship (SAR) analysis and molecular docking studies of newly synthesized compounds were also discussed, as well as the predicted physicochemical properties.     

Unsymmetrically disubstituted urea derivatives: A potent class of antiglycating agents

A series of unsymmetrically disubstituted urea derivatives 1–28 has been synthesized and screened for their antiglycation activity in vitro. Compounds 26 (IC₅₀ = 4.26 ± 0.25 μM), 1 (IC₅₀ = 5.8 ± 0.08 μM), 22 (IC₅₀ = 4.26 ± 0.25 μM), 6 (IC₅₀ = 6.4 ± 0.02 μM), 5 (IC₅₀ = 6.6 ± 0.26 μM), 2 (IC₅₀ = 7.02 ± 0.31 μM), 3 (IC₅₀ = 7.14 ± 0.84 μM), 27 (IC₅₀ = 7.27 ± 0.36 μM), 4 (IC₅₀ = 8.16 ± 1.04 μM), 21 (IC₅₀ = 8.4 ± 0.15 μM), 23 (IC₅₀ = 9.0 ± 0.35 μM) and 13 (IC₅₀ = 15.22 ± 6.7 μM) showed an excellent antiglycation activity far better than the standard (rutin, IC₅₀ = 41.9 ± 2.3 μM). This study thus provides a series of potential molecules for further studies of antiglycation agents.     

Terpenoids with cytotoxic activity from the branches and leaves of Pyrus pashia

Twenty terpenoids, including a new triterpenoid (1) and a new monoterpenoid (20), were isolated from the branches and leaves of Pyrus pashia. The structures of two new compounds were determined to be 2α, 3β, 27-trihydroxyolean-12-en-28-oic acid (1) and (4α)-3-(5,5-dimethyltetrahydrofuranyl)-1-buten-3-ol 3-O-β-d-glucopyranoside (20) on the basis of spectroscopic analysis (IR, HRESIMS, 1D and 2D NMR) and chemical method. Some of the isolated compounds were evaluated for their cytotoxic activity against a panel of human cancer cell lines by MTT assay, using cisplatin as a positive control. Compound 14 exhibited cytotoxic activities against A549 (IC₅₀ = 19.18 ± 4.26 μM), Hela (IC₅₀ = 12.56 ± 3.89 μM), SGC7901 (IC₅₀ = 10.48 ± 1.95 μM) and NHI-1975 (IC₅₀ = 7.38 ± 2.31 μM) cell lines as well as compound 12 displayed cytotoxic activities against A549 (IC₅₀ = 14.71 ± 1.47 μM) and Hela (IC₅₀ = 12.22 ± 1.88 μM) cell lines.     

Phosphoramidate derivatives of acyclovir: Synthesis and antiviral activity in HIV-1 and HSV-1 models in vitro

The antiviral activity against HIV and HSV and the chemical stability of ACV phosphoramidate derivatives were studied. The phosphoramidates of ACV demonstrated moderate activity. The best compound appeared to be 9-(2-hydroxymethyl)guanine phosphoromonomorpholidate (7), which inhibited virus replication in pseudo-HIV-1 particles by 50% at 50 μM. It also inhibited replication of wild-type HSV-1 (9.7 μM) as well as an acyclovir-resistant strain (25 μM). None of the synthesised compounds showed any cytotoxicity.     

Protection of oxidative stress induced apoptosis in osteosarcoma cells by dihydromyricetin through down-regulation of caspase activation and up-regulation of BcL-2

Current study was aimed to investigate the effect of dihydromyricetin on hydrogen peroxide induced oxidative stress in the osteosarcoma cells. MTT assay showed that hydrogen peroxide treatment at a concentration of 100 μM caused a significant (p < 0.005) reduction in the viability of MG63 cells. However, reduction in cell viability caused by 100 μM concentration of hydrogen peroxide was completely prevented on incubation with 30 μM dose of dihydromyricetin. Treatment with 100 μM concentration of hydrogen peroxide for 24 h led to condensation of chromatin material, rounding of cell shape and detachment of cells. The results from flow cytometry using annexin V-FITC and PI double staining showed apoptosis induction in 47.84 ± 5.21% cells on treatment with 100 μM concentration of hydrogen peroxide compared to 2.32 ± 0.54% in controlcells. The apoptotic alterations in MG63 cell morphology were prevented significantly on pre-treatment with 30 μM doses of dihydromyricetin for 48 h. Annexin V-FITC and PI staining showed reduction of hydrogen peroxide induced apoptotic cell percentage to 3.07 ± 0.86% on pre-treatment of MG63 cells with 30 μM dose of dihydromyricetin. Western blot analysis showed a significant increase in the activation of caspase-3 and -9 on treatment of MG63 cells for 24 h with 100 μM concentration of hydrogen peroxide. The expression level of Bcl-2 was decreased significantly by 100 μM concentration of hydrogen peroxide in MG63 cells. However, pre-treatment of MG63 cells with 30 μM dose of dihydromyricetin for 48 h significantly prevented hydrogen peroxide induced increase in caspase-3 and -9 levels and reduction in Bcl-2 level. Thus dihydromyricetin prevents hydrogen peroxide induced reduction in viability and induction of apoptosis in MG63 cells through down-regulation of caspase activation and up-regulation of Bcl-2 levels.     

Synthesis,biological evaluation,and docking studies of novel heterocyclic diaryl compounds as selective COX-2 inhibitors

Three novel series of diaryl heterocyclic derivatives bearing the 2-oxo-5H-furan, 2-oxo-3H-1,3-oxazole, and 1H-pyrazole moieties as the central heterocyclic ring were synthesized and their in vitro inhibitory activities on COX-1 and COX-2 isoforms were evaluated using a purified enzyme assay. The 2-oxo-5H-furan derivative 6b was identified as potent COX inhibitor with selectivity toward COX-1 (COX-1 IC₅₀ = 0.061 μM and COX-2 IC₅₀ = 0.325 μM; selectivity index (SI) = 0.19). Among the 1H-pyrazole derivatives, 11b was found to be a potent COX-2 inhibitor, about 38 times more potent than Rofecoxib (COX-2 IC₅₀ = 0.011 μM and 0.398 μM, respectively), but showed no selectivity for COX-2 isoform. Compound 11c demonstrated strong and selective COX-2 inhibitory activity (COX-1 IC₅₀ = 1 μM, COX-2 IC₅₀ = 0.011 μM; SI = ～92). Molecular docking studies of compounds 6b and 11b–d into the binding sites of COX-1 and COX-2 allowed to shed light on the binding mode of these novel COX inhibitors.     

Effects of endogenous cannabinoid anandamide on cardiac Na+/Ca2+ exchanger

Endocannabinoid anandamide (N-arachidonoyl ethanolamide; AEA) has been shown to cause negative inotropic and antiarrhythmic effects in ventricular myocytes. In this study, using whole-cell patch clamp technique, we have investigated the effects of AEA on cardiac Na⁺/Ca²⁺ exchanger (NCX1)-mediated currents. AEA suppressed NCX1 with an IC₅₀ value of 4.7 μM. Both inward and outward components of exchanger currents were suppressed by AEA equally. AEA inhibition was mimicked by the metabolically stable analogue, methanandamide (metAEA, 10 μM) while it was not influenced by inhibition of fatty acid amide hydrolase with 1 μM URB597 incubation. The effect of AEA, was not altered in the presence of cannabinoid receptor 1 and 2 antagonists AM251 (1 μM) and AM630 (1 μM), respectively. In addition, inhibition by AEA remained unchanged after pertussis toxin (PTX, 2 μg/ml) treatment or following the inclusion of GDP-β-S (1 mM) in pipette solution. Currents mediated by NCX1 expressed in HEK-293 cells were also inhibited by 10 μM AEA a partially reversible manner. Confocal microscopy images indicated that the intensity of YFP-NCX1 expression on cell surface was not altered by AEA. Collectively, the results indicate that AEA directly inhibits the function of NCX1 in rat ventricular myocytes and in HEK-293 cells expressing NCX1.     

Identification of novel acetylcholinesterase inhibitors: Indolopyrazoline derivatives and molecular docking studies

The synthesis of novel indolopyrazoline derivatives (P1-P4 and Q1-Q4) has been characterized and evaluated as potential anti-Alzheimer agents through in vitro Acetylcholinesterase (AChE) inhibition and radical scavenging activity (antioxidant) studies. Specifically, Q3 shows AChE inhibition (IC₅₀: 0.68 ± 0.13 μM) with strong DPPH and ABTS radical scavenging activity (IC₅₀: 13.77 ± 0.25 μM and IC₅₀: 12.59 ± 0.21 μM), respectively. While P3 exhibited as the second most potent compound with AChE inhibition (IC₅₀: 0.74 ± 0.09 μM) and with DPPH and ABTS radical scavenging activity (IC₅₀: 13.52 ± 0.62 μM and IC₅₀: 13.13 ± 0.85 μM), respectively. Finally, molecular docking studies provided prospective evidence to identify key interactions between the active inhibitors and the AChE that furthermore led us to the identification of plausible binding mode of novel indolopyrazoline derivatives. Additionally, in-silico ADME prediction using QikProp shows that these derivatives fulfilled all the properties of CNS acting drugs. This study confirms the first time reporting of indolopyrazoline derivatives as potential anti-Alzheimer agents.     

Structure–activity relationship studies of antiplasmodial aminomethylthiazoles

Structure–activity relationship (SAR) studies around a previously reported antimalarial aminomethylthiazole pyrazole carboxamide 1 are reported. Several analogues were synthesised and profiled for in vitro antiplasmodial activity against the drug-sensitive Plasmodium falciparum malaria parasite strain, NF54. Although all the reported analogues exhibited inferior in vitro antiplasmodial activity (IC₅₀ = 0.125–173 μM) relative to compound 1 (IC₅₀ = 0.0203 μM), one analogue, compound 5a, retained submicromolar activity (IC₅₀ = 0.125 μM).     

High paternal testosterone may protect against postpartum depressive symptoms in fathers,but confer risk to mothers and children

Following the birth of an infant, decreases in testosterone and increases in depressive symptoms have been observed in fathers. Paternal testosterone may reflect fathers' investment in pair-bonding and paternal caregiving and, as such, may be associated with maternal and familial well-being. This study tests associations between paternal testosterone, paternal and maternal postpartum depressive symptoms, and subsequent family functioning.Within 149 couples, fathers provided testosterone samples when infants were approximately nine months old and both parents reported on postpartum depressive symptoms at two, nine, and 15 months postpartum. Fathers with lower aggregate testosterone reported more depressive symptoms at two and nine months postpartum. Mothers whose partners had higher evening testosterone reported more depressive symptoms at nine and 15 months postpartum. Maternal relationship satisfaction mediated this effect, such that mothers with higher testosterone partners reported more relationship dissatisfaction, which in turn predicted more maternal depressive symptoms. Higher paternal testosterone and paternal depressive symptoms at nine months postpartum each independently predicted greater fathering stress at 15 months postpartum. Higher paternal testosterone also predicted more mother-reported intimate partner aggression at 15 months postpartum. In addition to linear relationships between testosterone and depression, curvilinear relationships emerged such that fathers with both low and high testosterone at nine months postpartum reported more subsequent (15-month) depressive symptoms and fathering stress.In conclusion, whereas higher paternal testosterone may protect against paternal depression, it contributed to maternal distress and suboptimal family outcomes in our sample. Interventions that supplement or alter men's testosterone may have unintended consequences for family well-being.