This document discusses steroidal hormones and contraceptive agents. It summarizes the hormones produced by the adrenal cortex, including glucocorticoids like cortisol and androgens. It also discusses the female sex hormones estrogen and progesterone, how they work together in the menstrual cycle, and examples of natural and synthetic estrogens. The document further summarizes the male sex hormone testosterone, anabolic androgens derived from testosterone, and anti-androgens used to treat conditions like prostate cancer.
sex-hormones belong to the steroid class of compounds and are produced in the gonads, i.e., testes in the male and ovaries in the female. In fact, their activity seems to be controlled and monitored by the hormones that are produced in the interior.
These slides contain the information about Estrogen, its basic pharmacology, its synthesis in human body, Functions of estrogen, role in female puberty, Agonists of estrogen and antagonists of estrogen, also contain detail of the receptors associated with the estrogen functioning.
sex-hormones belong to the steroid class of compounds and are produced in the gonads, i.e., testes in the male and ovaries in the female. In fact, their activity seems to be controlled and monitored by the hormones that are produced in the interior.
These slides contain the information about Estrogen, its basic pharmacology, its synthesis in human body, Functions of estrogen, role in female puberty, Agonists of estrogen and antagonists of estrogen, also contain detail of the receptors associated with the estrogen functioning.
This course provides an overview of the stages involved in the Phase I and Phase II metabolism of steroids in the Human body. Find out about the enzymes involved and how they modify the steroidal backbone.
Created by James Campbell and David Takapu (Undergraduates)
Edited by Margaret Hilton
Honors Organic Chemistry
Chem 2321 (Sigman), 2013, University of Utah
INTRODUCTION OF STEROIDS,
SAR OF STEROIDS
MECHANISM OF ACTION
CLASSIFICATION OF STEROIDS
STEROLS
SYNTHESIS OF CHOLESTEROL
STEROID HORMONES
BILE ACIDS
CONCLUSION
Here is a short an detailed explanation on nomenclature of steroids for pharmacy students. It includes all the points necessary for the topic along with an example for better understanding
Steroid hormones can be grouped into 2 classes, corticosteroids (typically made in the adrenal cortex, hence cortico-) and sex steroids (typically made in the gonads or placenta).
This course provides an overview of the stages involved in the Phase I and Phase II metabolism of steroids in the Human body. Find out about the enzymes involved and how they modify the steroidal backbone.
Created by James Campbell and David Takapu (Undergraduates)
Edited by Margaret Hilton
Honors Organic Chemistry
Chem 2321 (Sigman), 2013, University of Utah
INTRODUCTION OF STEROIDS,
SAR OF STEROIDS
MECHANISM OF ACTION
CLASSIFICATION OF STEROIDS
STEROLS
SYNTHESIS OF CHOLESTEROL
STEROID HORMONES
BILE ACIDS
CONCLUSION
Here is a short an detailed explanation on nomenclature of steroids for pharmacy students. It includes all the points necessary for the topic along with an example for better understanding
Steroid hormones can be grouped into 2 classes, corticosteroids (typically made in the adrenal cortex, hence cortico-) and sex steroids (typically made in the gonads or placenta).
this presentation is about adrenal gland steroidogenesis and it also includes pathways of testosterone synthesis and its enzymes and mecahnism of actions
Multi-source connectivity as the driver of solar wind variability in the heli...Sérgio Sacani
The ambient solar wind that flls the heliosphere originates from multiple
sources in the solar corona and is highly structured. It is often described
as high-speed, relatively homogeneous, plasma streams from coronal
holes and slow-speed, highly variable, streams whose source regions are
under debate. A key goal of ESA/NASA’s Solar Orbiter mission is to identify
solar wind sources and understand what drives the complexity seen in the
heliosphere. By combining magnetic feld modelling and spectroscopic
techniques with high-resolution observations and measurements, we show
that the solar wind variability detected in situ by Solar Orbiter in March
2022 is driven by spatio-temporal changes in the magnetic connectivity to
multiple sources in the solar atmosphere. The magnetic feld footpoints
connected to the spacecraft moved from the boundaries of a coronal hole
to one active region (12961) and then across to another region (12957). This
is refected in the in situ measurements, which show the transition from fast
to highly Alfvénic then to slow solar wind that is disrupted by the arrival of
a coronal mass ejection. Our results describe solar wind variability at 0.5 au
but are applicable to near-Earth observatories.
A brief information about the SCOP protein database used in bioinformatics.
The Structural Classification of Proteins (SCOP) database is a comprehensive and authoritative resource for the structural and evolutionary relationships of proteins. It provides a detailed and curated classification of protein structures, grouping them into families, superfamilies, and folds based on their structural and sequence similarities.
Nutraceutical market, scope and growth: Herbal drug technologyLokesh Patil
As consumer awareness of health and wellness rises, the nutraceutical market—which includes goods like functional meals, drinks, and dietary supplements that provide health advantages beyond basic nutrition—is growing significantly. As healthcare expenses rise, the population ages, and people want natural and preventative health solutions more and more, this industry is increasing quickly. Further driving market expansion are product formulation innovations and the use of cutting-edge technology for customized nutrition. With its worldwide reach, the nutraceutical industry is expected to keep growing and provide significant chances for research and investment in a number of categories, including vitamins, minerals, probiotics, and herbal supplements.
Introduction:
RNA interference (RNAi) or Post-Transcriptional Gene Silencing (PTGS) is an important biological process for modulating eukaryotic gene expression.
It is highly conserved process of posttranscriptional gene silencing by which double stranded RNA (dsRNA) causes sequence-specific degradation of mRNA sequences.
dsRNA-induced gene silencing (RNAi) is reported in a wide range of eukaryotes ranging from worms, insects, mammals and plants.
This process mediates resistance to both endogenous parasitic and exogenous pathogenic nucleic acids, and regulates the expression of protein-coding genes.
What are small ncRNAs?
micro RNA (miRNA)
short interfering RNA (siRNA)
Properties of small non-coding RNA:
Involved in silencing mRNA transcripts.
Called “small” because they are usually only about 21-24 nucleotides long.
Synthesized by first cutting up longer precursor sequences (like the 61nt one that Lee discovered).
Silence an mRNA by base pairing with some sequence on the mRNA.
Discovery of siRNA?
The first small RNA:
In 1993 Rosalind Lee (Victor Ambros lab) was studying a non- coding gene in C. elegans, lin-4, that was involved in silencing of another gene, lin-14, at the appropriate time in the
development of the worm C. elegans.
Two small transcripts of lin-4 (22nt and 61nt) were found to be complementary to a sequence in the 3' UTR of lin-14.
Because lin-4 encoded no protein, she deduced that it must be these transcripts that are causing the silencing by RNA-RNA interactions.
Types of RNAi ( non coding RNA)
MiRNA
Length (23-25 nt)
Trans acting
Binds with target MRNA in mismatch
Translation inhibition
Si RNA
Length 21 nt.
Cis acting
Bind with target Mrna in perfect complementary sequence
Piwi-RNA
Length ; 25 to 36 nt.
Expressed in Germ Cells
Regulates trnasposomes activity
MECHANISM OF RNAI:
First the double-stranded RNA teams up with a protein complex named Dicer, which cuts the long RNA into short pieces.
Then another protein complex called RISC (RNA-induced silencing complex) discards one of the two RNA strands.
The RISC-docked, single-stranded RNA then pairs with the homologous mRNA and destroys it.
THE RISC COMPLEX:
RISC is large(>500kD) RNA multi- protein Binding complex which triggers MRNA degradation in response to MRNA
Unwinding of double stranded Si RNA by ATP independent Helicase
Active component of RISC is Ago proteins( ENDONUCLEASE) which cleave target MRNA.
DICER: endonuclease (RNase Family III)
Argonaute: Central Component of the RNA-Induced Silencing Complex (RISC)
One strand of the dsRNA produced by Dicer is retained in the RISC complex in association with Argonaute
ARGONAUTE PROTEIN :
1.PAZ(PIWI/Argonaute/ Zwille)- Recognition of target MRNA
2.PIWI (p-element induced wimpy Testis)- breaks Phosphodiester bond of mRNA.)RNAse H activity.
MiRNA:
The Double-stranded RNAs are naturally produced in eukaryotic cells during development, and they have a key role in regulating gene expression .
THE IMPORTANCE OF MARTIAN ATMOSPHERE SAMPLE RETURN.Sérgio Sacani
The return of a sample of near-surface atmosphere from Mars would facilitate answers to several first-order science questions surrounding the formation and evolution of the planet. One of the important aspects of terrestrial planet formation in general is the role that primary atmospheres played in influencing the chemistry and structure of the planets and their antecedents. Studies of the martian atmosphere can be used to investigate the role of a primary atmosphere in its history. Atmosphere samples would also inform our understanding of the near-surface chemistry of the planet, and ultimately the prospects for life. High-precision isotopic analyses of constituent gases are needed to address these questions, requiring that the analyses are made on returned samples rather than in situ.
Slide 1: Title Slide
Extrachromosomal Inheritance
Slide 2: Introduction to Extrachromosomal Inheritance
Definition: Extrachromosomal inheritance refers to the transmission of genetic material that is not found within the nucleus.
Key Components: Involves genes located in mitochondria, chloroplasts, and plasmids.
Slide 3: Mitochondrial Inheritance
Mitochondria: Organelles responsible for energy production.
Mitochondrial DNA (mtDNA): Circular DNA molecule found in mitochondria.
Inheritance Pattern: Maternally inherited, meaning it is passed from mothers to all their offspring.
Diseases: Examples include Leber’s hereditary optic neuropathy (LHON) and mitochondrial myopathy.
Slide 4: Chloroplast Inheritance
Chloroplasts: Organelles responsible for photosynthesis in plants.
Chloroplast DNA (cpDNA): Circular DNA molecule found in chloroplasts.
Inheritance Pattern: Often maternally inherited in most plants, but can vary in some species.
Examples: Variegation in plants, where leaf color patterns are determined by chloroplast DNA.
Slide 5: Plasmid Inheritance
Plasmids: Small, circular DNA molecules found in bacteria and some eukaryotes.
Features: Can carry antibiotic resistance genes and can be transferred between cells through processes like conjugation.
Significance: Important in biotechnology for gene cloning and genetic engineering.
Slide 6: Mechanisms of Extrachromosomal Inheritance
Non-Mendelian Patterns: Do not follow Mendel’s laws of inheritance.
Cytoplasmic Segregation: During cell division, organelles like mitochondria and chloroplasts are randomly distributed to daughter cells.
Heteroplasmy: Presence of more than one type of organellar genome within a cell, leading to variation in expression.
Slide 7: Examples of Extrachromosomal Inheritance
Four O’clock Plant (Mirabilis jalapa): Shows variegated leaves due to different cpDNA in leaf cells.
Petite Mutants in Yeast: Result from mutations in mitochondrial DNA affecting respiration.
Slide 8: Importance of Extrachromosomal Inheritance
Evolution: Provides insight into the evolution of eukaryotic cells.
Medicine: Understanding mitochondrial inheritance helps in diagnosing and treating mitochondrial diseases.
Agriculture: Chloroplast inheritance can be used in plant breeding and genetic modification.
Slide 9: Recent Research and Advances
Gene Editing: Techniques like CRISPR-Cas9 are being used to edit mitochondrial and chloroplast DNA.
Therapies: Development of mitochondrial replacement therapy (MRT) for preventing mitochondrial diseases.
Slide 10: Conclusion
Summary: Extrachromosomal inheritance involves the transmission of genetic material outside the nucleus and plays a crucial role in genetics, medicine, and biotechnology.
Future Directions: Continued research and technological advancements hold promise for new treatments and applications.
Slide 11: Questions and Discussion
Invite Audience: Open the floor for any questions or further discussion on the topic.
Richard's aventures in two entangled wonderlandsRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
The increased availability of biomedical data, particularly in the public domain, offers the opportunity to better understand human health and to develop effective therapeutics for a wide range of unmet medical needs. However, data scientists remain stymied by the fact that data remain hard to find and to productively reuse because data and their metadata i) are wholly inaccessible, ii) are in non-standard or incompatible representations, iii) do not conform to community standards, and iv) have unclear or highly restricted terms and conditions that preclude legitimate reuse. These limitations require a rethink on data can be made machine and AI-ready - the key motivation behind the FAIR Guiding Principles. Concurrently, while recent efforts have explored the use of deep learning to fuse disparate data into predictive models for a wide range of biomedical applications, these models often fail even when the correct answer is already known, and fail to explain individual predictions in terms that data scientists can appreciate. These limitations suggest that new methods to produce practical artificial intelligence are still needed.
In this talk, I will discuss our work in (1) building an integrative knowledge infrastructure to prepare FAIR and "AI-ready" data and services along with (2) neurosymbolic AI methods to improve the quality of predictions and to generate plausible explanations. Attention is given to standards, platforms, and methods to wrangle knowledge into simple, but effective semantic and latent representations, and to make these available into standards-compliant and discoverable interfaces that can be used in model building, validation, and explanation. Our work, and those of others in the field, creates a baseline for building trustworthy and easy to deploy AI models in biomedicine.
Bio
Dr. Michel Dumontier is the Distinguished Professor of Data Science at Maastricht University, founder and executive director of the Institute of Data Science, and co-founder of the FAIR (Findable, Accessible, Interoperable and Reusable) data principles. His research explores socio-technological approaches for responsible discovery science, which includes collaborative multi-modal knowledge graphs, privacy-preserving distributed data mining, and AI methods for drug discovery and personalized medicine. His work is supported through the Dutch National Research Agenda, the Netherlands Organisation for Scientific Research, Horizon Europe, the European Open Science Cloud, the US National Institutes of Health, and a Marie-Curie Innovative Training Network. He is the editor-in-chief for the journal Data Science and is internationally recognized for his contributions in bioinformatics, biomedical informatics, and semantic technologies including ontologies and linked data.
1. Chemistry of steroidal hormones and
contraceptive agents
Shree dhanvantary pharmacy college
Prepared by: arzoo dharasandia
Guided by: Stephen sir
1
2. Adrenocortical Hormones
Adrenal gland:
Medulla:
produces Epinephrine
(stimulated by sympathetic
impulse)
Cortex:
Zona glomerulosa – produces
Aldosterone
(stimulated by Angiotensin II and
ACTH)
Zona fasciculata – produces
Glucocorticoids
(stimulated by ACTH =
Corticotropin)
Zona reticularis – produces
Androgens
2
3. Adrenocortical Hormones
Glucocorticoids (GC):
Inhibit all phases of inflammatory reaction
Promote fetal development (lungs)
Unregulate lipocortin => inhibits PLA2 => no PG and LT synthesis
Undesirable effects of increased GC:
Immune suppression
Increased glucose release (=> “steroid diabetes”)
Glucose coverted to fat => adiposity
Increased protein catabolism => muscle atrophy
Salt and water retention (increased GC lead to reduction in ACTH =>
decreases levels of aldosterone) => hypertension
Osteoporosis
3
4. Adrenocortical Hormones
Glucocorticoids (GC):
Hydrocortison (= Cortisol)
Main glucocortocoid in humans
Also binds mineralocorticoid receptor
(Cortison does NOT)
Used for replacement therapy (Addison’s Disease)
4
5. Topical Hydrocortisone
Hydrocortisone is a topical steroid. It reduces the
actions of chemicals in the body that cause
inflammation, redness, and swelling.
Hydrocortisone topical is used to treat inflammation of
the skin caused by a number of conditions such as
allergic reactions, eczema, or psoriasis.
Hydrocortisone topical may also be used for other
purposes .it do not give any antibacterial activity.
5
6. Hydrocortisone oral
Hydrocortisone is also used
to treat low hydrocortisone
levels caused by diseases of
the adrenal gland (such as
Addison's disease,
adrenocortical
insufficiency).
Corticosteroids are needed
in many ways for the body
to function well. They are
important for salt and water
balance and keeping
blood pressure normal.
6
8. Hormones involved in ovulation process
Gonadotropin Releasing Hormone
(GnRH) = Gonadoliberin
stimulates release of
Follicle stimulating hormone
(FSH) = Follitropin
and
Luteinising Hormone
(LH) = Lutropin
which trigger production of
Estrogens (E) and Gestagens (G)
which in turn negatively regulate
Pituitary (E+G) and Hypothalamus (G)
hormone production
8
9. How estrogen and progesterone are produced and
involved in female reproductive cycle
Cycle length varies from 21-35 days
Menstruation 3-6 days
First (= Proliferative) phase:
Variable (7-21 days)
FSH and LH promote follicle development
One follicle becomes the Graafian follicle
(the rest degenerate)
Graaffian Follicle:
Consists of thecal and granulosa cells
which surround the ovum
FSH-stimulated granulosa cells produce
estrogens from androgen precursors
generated by LH-stimulated thecal cells
Estrogens are responsible for the
proliferative phase: increase in thickness
and vascularity of endometrium; secretion
of protein+ carbo-rich mucus
Constant low estrogen inhibits LH/FSH production BUT high estrogen cause surge
of LH production => swelling and rupture of Graafian follicle = Ovulation
9
10. Sex Steroids
Female reproductive cycle
Second (= Secretory) phase:
Secretory phase constant (~ 14 days)
LH-stimulated ruptured follicle develops
into Corpus luteum which secrets
Progesterone
Progesterone (Pg) is responsible for the
secretory phase: endometrium becomes
suitable for implantation; mucus thickens
Thermogenic effects of Pg =>
body temperature increase 0.5º C
Without implantation: Pg secretion stops
=> menstruation is triggered
With implantation: continued Pg
production
which (via inhibition of LH and FSH prod.)
blocks further ovulation
Chorion (“precursor” of placenta)
secretes
human chorionic gonadotropin (HCG)
which
maintains endometrium lining throughout
pregnancy (HCG -> see pregnancy test)
10
12. ESTROGENS
All produced from androgen precursors
Three main endogenous estrogens:
Estradiol
Primary estrogen in humans
Breast development
Improving bone density
Growth of the uterus
Accelerating bone maturation
Development of the endometrium to support pregnancy
Promoting vaginal mucosal thickness and secretions
Increase HDL
Estrone
1/3 active than estradiol
Estriol
only during pregnancy (made by fetus)
12
14. Sar of estrogens 14
Aromatic ring with C-3-OH is essential for activity.
Steroidal structures is not essential for activity.
The intensity of activity changesif route of administration
changes, e.g.,for oral route: Estriol > estradiol > estrone.
For subcutaneous route: estradiol > estrone > estriol.
Alkylation of the aromatic ring decrease the activity.
The 17β-hydroxyl with constant distance from 3-OH is
essential for activity.
The group between the two hydroxyl must be
hydrophobic.
Unsaturation of ring B decreases the activity.
17α- and 16 position when modified enhance the activity.
Example: mestranol.
16. Estradiol:
Estradiol is rapidaly oxidized in the liver to form estrone,
which is ineffective.
Ethinyl estradiol:
15- 20 more potent than estradiol orally.
Adding a 17β-ethiny to estradiol blocks this oxidation and
makes the compound orally active.
16
17. Synthetic or non-steroidal estrogens
Diethylstilbesterol:
The trans form is the active
one.
Advantages:
As active as Estradiol.
Longer duration of action.
Orally active
Cheap.
Disadvantages:
Increase the risk of uterine
cancer.
Uses:
Treatment of prostate cancer.
17
OH
HO
18. ESTROGEN ANTAGONISTS
Tamoxifen
Antiestrogenic effects on mammary
tissue
Weak estrogenic effects on bone and
lipid metabolism
Clomiphene
Inhibits estrogen binding in the pituitary
=> prevention of negative feedback=>
ovulation
Clinical uses of anti-estrogens:
Breast cancer therapy (Tamoxifen)
Infertility (Clomiphen)
18
19. progesterone
Progesterone
Inhibits rhythmic contractions of the myometrium
Not suitable for oral administration
(rapid hepatic elimination) => stable derivatives:
Hydroxyprogesterone
Medroxyprogesterone
19
20. Sar of progesterone
Steroidal nucleus essential for activity.
Have some androgenic activity.
Removal of the 19 CH3 increase activity.
Unsaturation of ring B or C increase the activity.e.g., megestrole
acetate.
Removal of the keto function remove androgenic activity.
20
26. androgens
Testosterone
Primary androgen in humans
Possesses androgenic and anabolic effects:
Androgenic effects:
Growth and development of male sex organs
Important for (male) sex drive and performance
Development of secondary sexual characteristics
Important role in spermatogenesis
Anabolic effects:
Development of muscle mass
Reverse catabolic or tissue-depleting processes
Dihydro-Testosterone
Active metabolite
Mediates most of testosterone actions
CH3
OH
O
CH3
CH3
OH
O
CH3
H
26
27. androgens
Testosterone
Hepatic elimination after oral administration
Also short half-life after injection => ester derivatives:
Proprionate, enanthate, cypionate…
Fluoxymesterone
Hepatic elimination after oral administration
CH3
OH
O
CH3
OH
F
CH3
CH3
OH
O
CH3
R
27
28. Anabolic androgens
Testosterone derivatives: anabolic effects dominant
Nandrolone
Injection
Stanozolol
oral administration
CH3
OH
O
CH3
H
OH
O
CH3
CH3
OH
N
CH3
CH3
NH
H
28
29. Anti androgens
Flutamide
Non-steroidal receptor antagonist
Used in prostate cancer treatment
Finasteride
Inhibits 5α-reductase => prevent conversion of
testosterone into the more potent dihydrotestosterone (DHT)
Used to treat prostate gland enlargement and hair loss
(bald man have higher average levels of DHT)
NH
CF3
O
CH3
NO2
CH3
CH3
CH3
N
H
O
O
N
H
CH3
CH3
CH3
H
29
